Is STS p.Phe212Ser (c.635T>C) pathogenic?

STS p.Phe212Ser (c.635T>C) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-07). AlphaMissense: likely benign (0.1205); Absent from gnomAD v4.1.

How common is STS p.Phe212Ser (c.635T>C) in the general population?

STS p.Phe212Ser (c.635T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STS p.Phe212Ser (c.635T>C)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

STS p.Phe212Ser

c.635T>C · rs2518623818 · VCV2819306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -5.97	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 0.26	GERP 4
Regional constraint	o/e 0.79	unconstrained · MANE · 72 kb · p 0.00048 · regional, not allelic
Overall
CADD	15.29	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 F217S vs ClinVar F212S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STS
Protein: p.Phe212Ser
Coding: c.635T>C
MANE Select: NM_001320752
dbSNP: rs2518623818
Type: single nucleotide variant
Location: chrX:7259601 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 217 UniProt numbering: an α-helix

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

Similar variants

STS p.Phe212fs Likely pathogenic ★ same residue
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

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-phe212ser (accessed [today's date]).

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