Is STS p.Val261Met (c.781G>A) pathogenic?

STS p.Val261Met (c.781G>A) is classified Likely benign in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0701); Ultra-rare (popmax 0.013%, amr); Associated with Inborn genetic diseases.

What condition is associated with STS p.Val261Met (c.781G>A)?

STS p.Val261Met (c.781G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Val261Met (c.781G>A) in the general population?

STS p.Val261Met (c.781G>A) is ultra-rare (popmax 0.013%, amr) (gnomAD).

What do computational predictors say about STS p.Val261Met (c.781G>A)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

STS p.Val261Met

c.781G>A · VCV4632436

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -6.38	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 0.06	GERP -0.89
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	1.074	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V266M vs ClinVar V261M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.013% Admixed American · 6/46,043 alleles

Filtering AF 0.00567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00386%

Overall 0.000661% 8/1,211,162 alleles · ultra-rare exomes 8/1,097,493 · genomes 0/113,669 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.013%	7,674
South Asian	0.00351%	28,491

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: STS
Protein: p.Val261Met
Coding: c.781G>A
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7259747 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 266 UniProt numbering: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STS p.Val261Leu Uncertain significance ★ ⚠ same residue
STS p.Val261Ala Likely benign ★ same residue
STS p.Arg381Ser Uncertain significance ★★ ⚠ same condition
STS p.Asp397Asn Uncertain significance ★★ ⚠ same condition
STS p.Arg578His Benign/Likely benign ★★ same condition
STS c.943+5G>A Conflicting classifications of pathogenicity ★ same condition
STS p.Ala295Val Uncertain significance ★ ⚠ same condition
STS p.Ala529Val Uncertain significance ★ ⚠ same condition

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/sts-p-val261met (accessed [today's date]).

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