Is STS p.Tyr252Phe (c.755A>T) pathogenic?

STS p.Tyr252Phe (c.755A>T) is classified Benign in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0894%, afr).

How common is STS p.Tyr252Phe (c.755A>T) in the general population?

STS p.Tyr252Phe (c.755A>T) is ultra-rare (popmax 0.0894%, afr) (gnomAD).

What do computational predictors say about STS p.Tyr252Phe (c.755A>T)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

STS p.Tyr252Phe

c.755A>T · VCV3709572

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0894%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -5.55	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 3.8	GERP 3.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	3.212	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 Y257F vs ClinVar Y252F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0894% African / African-American · 51/57,032 alleles

Filtering AF 0.0699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.00488% 59/1,209,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0894%	1,118
Admixed American	0.00876%	11,418
Remaining individualsnot grpmax-eligible	0.0084%	11,899

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.Tyr252Phe
Coding: c.755A>T
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7259721 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 252: a β-strand

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-tyr252phe (accessed [today's date]).

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