Is STS p.Asp322His (c.964G>C) pathogenic?

STS p.Asp322His (c.964G>C) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.2093); Very rare (popmax 0.00657%, amr); Associated with Inborn genetic diseases.

What condition is associated with STS p.Asp322His (c.964G>C)?

STS p.Asp322His (c.964G>C) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Asp322His (c.964G>C) in the general population?

STS p.Asp322His (c.964G>C) is very rare (popmax 0.00657%, amr) (gnomAD).

What do computational predictors say about STS p.Asp322His (c.964G>C)?

AlphaMissense predicts likely benign (score 0.2093) — an in-silico prediction, not a clinical call.

STS p.Asp322His

c.964G>C · VCV3323442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00657%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2093	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 3.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	17.33	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 D327H vs ClinVar D322H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00657% Admixed American · 3/45,660 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000883%

Overall 0.00132% 16/1,209,315 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00657%	15,220
Remaining individualsnot grpmax-eligible	0.0021%	47,552
European (non-Finnish)	0.00134%	74,558

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.Asp322His
Coding: c.964G>C
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7305066 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 322: 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.Asp322Asn 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
STS p.Arg179Ser 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-asp322his (accessed [today's date]).

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