SPRR2D

Chr 1

small proline rich protein 2D

NCBI Gene: 6703 ENSG00000163216 UniProt: P22532 OMIM: 617587

Predicted to be involved in female gonad development. Predicted to act upstream of or within response to estradiol. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Predicted to be involved in female gonad development. Predicted to act upstream of or within response to estradiol. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.93

Clinical Summary— SPRR2D

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 VUS of 17 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.016

Z-score -0.62

OE 1.59 (0.48–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.68Z-score

OE missense 1.31 (1.04–1.65)

51 obs / 39.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.59 (0.48–1.93)

0≤0.351.4

Missense OE?1.31 (1.04–1.65)

0≤0.61.4

Synonymous OE?1.73

0≤1.21.6

LoF obs/exp: 2 / 1.3Missense obs/exp: 51 / 39.0Syn Z: -2.26

This gene — mechanism propensity

0.90top 5%

GOF

0.75top 25%

LOF

0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

17 submitted variants in ClinVar

ClinVar

Classification Summary

VUS16

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	16	16
Likely Benign	1	1
Benign	0	0
Total	17	17

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap SPRR2D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →