Is STS p.Leu331Val (c.991C>G) pathogenic?

STS p.Leu331Val (c.991C>G) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.1032); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with STS p.Leu331Val (c.991C>G)?

STS p.Leu331Val (c.991C>G) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Leu331Val (c.991C>G) in the general population?

STS p.Leu331Val (c.991C>G) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about STS p.Leu331Val (c.991C>G)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

STS p.Leu331Val

c.991C>G · rs1485918787 · VCV2545019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -9.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP 2.9, phastCons 0.4
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	16.87	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 L336V vs ClinVar L331V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,615 alleles

Overall 0.000892% 1/112,100 alleles · very rare

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.Leu331Val
Coding: c.991C>G
MANE Select: NM_001320752
dbSNP: rs1485918787
Type: single nucleotide variant
Location: chrX:7305093 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB

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.Ala295Val Uncertain significance ★ ⚠ same condition
STS p.Ala529Val Uncertain significance ★ ⚠ same condition
STS p.Arg179Ser Uncertain significance ★ ⚠ same condition
STS p.Arg233Pro 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-leu331val (accessed [today's date]).

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