Is STS p.Ala295Val (c.884C>T) pathogenic?

STS p.Ala295Val (c.884C>T) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-12). AlphaMissense: likely benign (0.086); Ultra-rare (popmax 0.0125%, sas); Associated with Inborn genetic diseases.

What condition is associated with STS p.Ala295Val (c.884C>T)?

STS p.Ala295Val (c.884C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Ala295Val (c.884C>T) in the general population?

STS p.Ala295Val (c.884C>T) is ultra-rare (popmax 0.0125%, sas) (gnomAD).

What do computational predictors say about STS p.Ala295Val (c.884C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

STS p.Ala295Val

c.884C>T · VCV4177202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -5.31	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 1.2	GERP 4.8, phastCons 0.001
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	6.51	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A300V vs ClinVar A295V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% South Asian · 7/56,198 alleles

Filtering AF 0.00576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00108% 13/1,199,174 alleles · ultra-rare exomes 12/1,094,434 · genomes 1/104,740 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0125%	8,028
Remaining individualsnot grpmax-eligible	0.00423%	23,628
European (non-Finnish)	0.000449%	222,792

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.Ala295Val
Coding: c.884C>T
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7276028 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 300 UniProt numbering: a turn

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.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.Ala529Val Uncertain significance ★ ⚠ same condition
STS p.Arg179Ser Uncertain significance ★ ⚠ same condition
STS p.Arg233Pro Uncertain significance ★ ⚠ same condition
STS p.Arg325Ile 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-ala295val (accessed [today's date]).

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