CRYGC

Chr 2AD

crystallin gamma C

Also known as: CCL, CRYG3, CTRCT2

NCBI Gene: 1420 ENSG00000163254 UniProt: P07315 OMIM: 123680

This protein is a dominant structural component of the vertebrate eye lens that maintains lens transparency and refractive index. Mutations cause multiple types of congenital cataracts including Coppock-like cataract and zonular pulverulent cataract, which typically follow an autosomal dominant inheritance pattern. The gene shows low constraint against loss-of-function variants, consistent with the dominant inheritance pattern observed in cataract families.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 1.311 OMIM phenotype

Clinical Summary— CRYGC

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 52 VUS of 111 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.001

Z-score 0.93

OE 0.67 (0.36–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.16 (1.01–1.35)

127 obs / 109.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.67 (0.36–1.31)

0≤0.351.4

Missense OE?1.16 (1.01–1.35)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 6 / 9.0Missense obs/exp: 127 / 109.2Syn Z: -0.63

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCRYGC-related congenital cataractLOFAD

This gene — mechanism propensity

0.77top 25%

GOF

0.4282th %ile

LOF

0.3647th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic9

VUS52

Likely Benign16

Benign12

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	12	3	0	0	15
Likely Pathogenic	8	1	0	0	9
VUS	4	46	2	0	52
Likely Benign	0	3	9	4	16
Benign	0	2	7	3	12
Conflicting	—				6
Total	24	55	18	7	110

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

27 pathogenic / likely-pathogenic (of 34) ClinVar copy-number / structural variants overlap CRYGC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →