Is STS p.Val302Ile (c.904G>A) pathogenic?

STS p.Val302Ile (c.904G>A) is classified Benign in STS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0698); Common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about STS p.Val302Ile (c.904G>A)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

STS p.Val302Ile

Q: How common is STS p.Val302Ile (c.904G>A) in the general population?

STS p.Val302Ile (c.904G>A) is common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.904G>A · rs113416414 · VCV1282545

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.77%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -5.91	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 -3.4	GERP -1.4
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	0.503	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 V307I vs ClinVar V302I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.77% African / African-American · 3,765/55,627 alleles

Filtering AF 6.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.51%

Overall 0.393% 4,733/1,203,991 alleles · common exomes 2,581/1,096,698 · genomes 2,152/107,293 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.77%	15
Admixed American	0.95%	105
Remaining individualsnot grpmax-eligible	0.626%	160
Middle Eastern	0.556%	180
Ashkenazi Jewishnot grpmax-eligible	0.301%	332
South Asian	0.0266%	3,761
European (non-Finnish)	0.0154%	6,473

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.Val302Ile
Coding: c.904G>A
MANE Select: NM_001320752
dbSNP: rs113416414
Type: single nucleotide variant
Location: chrX:7276048 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 307 UniProt numbering: an α-helix

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

Similar variants

STS p.Gly354Arg Likely pathogenic ★★ same type
STS p.Arg381Ser Uncertain significance ★★ ⚠ same type
STS p.Asp397Asn Uncertain significance ★★ ⚠ same type
STS c.1082-55C>T Likely benign ★★ same type
STS c.1082-76G>A Benign ★★ same type
STS c.1241+15G>C Benign ★★ same type
STS c.138-9T>G Likely benign ★★ same type
STS c.383-16C>T Benign/Likely benign ★★ 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/sts-p-val302ile (accessed [today's date]).

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