Is STS p.Ser577Arg (c.1731C>G) pathogenic?

STS p.Ser577Arg (c.1731C>G) is classified Benign/Likely benign in STS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.135); Low-frequency (popmax 1.08%, afr).

How common is STS p.Ser577Arg (c.1731C>G) in the general population?

STS p.Ser577Arg (c.1731C>G) is low-frequency (popmax 1.08%, afr) (gnomAD).

What do computational predictors say about STS p.Ser577Arg (c.1731C>G)?

AlphaMissense predicts likely benign (score 0.135) — an in-silico prediction, not a clinical call.

STS p.Ser577Arg

c.1731C>G · rs151332463 · VCV445889

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.135 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.135	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP 2.4
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	10.53	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 S582R vs ClinVar S577R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% African / African-American · 618/57,337 alleles

Filtering AF 1.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.98%

Overall 0.0585% 705/1,205,555 alleles · low-frequency exomes 398/1,092,987 · genomes 307/112,568 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.101%	988
Middle Eastern	0.0965%	1,037
Admixed American	0.0594%	1,684
South Asian	0.0089%	11,236
European (non-Finnish)	0.000336%	297,699

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.Ser577Arg
Coding: c.1731C>G
MANE Select: NM_001320752
dbSNP: rs151332463
Type: single nucleotide variant
Location: chrX:7350255 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB

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-ser577arg (accessed [today's date]).

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