Is STS p.Asp413Gly (c.1238A>G) pathogenic?

STS p.Asp413Gly (c.1238A>G) is classified Benign in STS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-01). AlphaMissense: likely benign (0.1281); Rare (popmax 0.146%, nfe).

How common is STS p.Asp413Gly (c.1238A>G) in the general population?

STS p.Asp413Gly (c.1238A>G) is rare (popmax 0.146%, nfe) (gnomAD).

What do computational predictors say about STS p.Asp413Gly (c.1238A>G)?

AlphaMissense predicts likely benign (score 0.1281) — an in-silico prediction, not a clinical call.

STS p.Asp413Gly

c.1238A>G · rs141215364 · VCV707559

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1281 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.146%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1281	likely benign
REVEL	0.634	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Constraint at this position
Conservation	phyloP 8.8	GERP 6.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	23.5	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 D418G vs ClinVar D413G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.146% European (non-Finnish) · 1,306/894,877 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.12% 1,450/1,209,016 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.159%	629
European (non-Finnish)grpmax	0.146%	685
Remaining individualsnot grpmax-eligible	0.0631%	1,585
African / African-American	0.0298%	3,361
South Asian	0.0282%	3,546
Admixed American	0.0131%	7,616
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,025

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp413Gly
Coding: c.1238A>G
MANE Select: NM_001320752
dbSNP: rs141215364
Type: single nucleotide variant
Location: chrX:7325495 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB
Residue 413: an α-helix

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

Similar variants

STS p.Asp413Asn Uncertain significance ★ ⚠ 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-asp413gly (accessed [today's date]).

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