Is CST7 p.Val131Met (c.391G>A) pathogenic?

CST7 p.Val131Met (c.391G>A) is classified Uncertain significance in CST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.1589); Ultra-rare (popmax 0.066%, mid).

How common is CST7 p.Val131Met (c.391G>A) in the general population?

CST7 p.Val131Met (c.391G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about CST7 p.Val131Met (c.391G>A)?

AlphaMissense predicts likely benign (score 0.1589) — an in-silico prediction, not a clinical call.

CST7 p.Val131Met

c.391G>A · rs150607778 · VCV3078420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1589 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1589	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -1.9, phastCons 0.52
Regional constraint	o/e 1.08	unconstrained · MANE · 10 kb · p 0.29 · regional, not allelic
Overall
CADD	13.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00483% 78/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
South Asian	0.022%	4,554
African / African-American	0.016%	6,252
Remaining individualsnot grpmax-eligible	0.008%	12,501
Admixed American	0.00333%	30,015
European (non-Finnish)	0.00288%	34,706
East Asian	0.00223%	44,866

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CST7
Protein: p.Val131Met
Coding: c.391G>A
MANE Select: NM_003650
dbSNP: rs150607778
Type: single nucleotide variant
Location: chr20:24959665 (GRCh38)
Gene constraint: LOEUF 1.742 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.78 · 1 PDB
Residue 131: a β-strand; a disulfide bond

Full CST7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST7 p.Val131Gly Uncertain significance ★ ⚠ same residue
CST7 p.Ala9Val Uncertain significance ★ ⚠ same type
CST7 p.Arg33His Uncertain significance ★ ⚠ same type
CST7 p.Arg96Ser Uncertain significance ★ ⚠ same type
CST7 p.Asn61His Uncertain significance ★ ⚠ same type
CST7 p.Cys63Arg Uncertain significance ★ ⚠ same type
CST7 p.Cys99Ser Uncertain significance ★ ⚠ same type
CST7 p.Glu138Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cst7-p-val131met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown