CST2 encodes a secreted thiol protease inhibitor found at high levels in saliva, tears, and seminal plasma. The gene is not constrained against loss-of-function variants (LOEUF 1.94), and no Mendelian diseases have been definitively associated with CST2 mutations in current databases. Clinical significance of variants in this gene remains uncertain.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
20
P/LP submissions
0%
P/LP missense
1.94
LOEUF
DN
Mechanism· predicted
Clinical SummaryCST2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 43 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.94LOEUF
pLI 0.000
Z-score -1.25
OE 1.56 (0.891.94)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.12Z-score
OE missense 1.66 (1.441.90)
135 obs / 81.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.56 (0.891.94)
00.351.4
Missense OE1.66 (1.441.90)
00.61.4
Synonymous OE1.77
01.21.6
LoF obs/exp: 9 / 5.8Missense obs/exp: 135 / 81.2Syn Z: -3.53
DN
0.73top 25%
GOF
0.5465th %ile
LOF
0.2190th %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

77 submitted variants in ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS43
Likely Benign8
Benign2
17
Pathogenic
3
Likely Pathogenic
43
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
3
0
3
VUS
0
41
2
0
43
Likely Benign
0
5
3
0
8
Benign
0
1
1
0
2
Total04726073

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

View in ClinVar →

Protein Context — Lollipop Plot

CST2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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