Is STS p.Asp503Glu (c.1509T>G) pathogenic?

STS p.Asp503Glu (c.1509T>G) is classified Uncertain significance in STS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.8575); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with STS p.Asp503Glu (c.1509T>G)?

STS p.Asp503Glu (c.1509T>G) is associated with Inborn genetic diseases (ClinVar).

How common is STS p.Asp503Glu (c.1509T>G) in the general population?

STS p.Asp503Glu (c.1509T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STS p.Asp503Glu (c.1509T>G)?

AlphaMissense predicts likely pathogenic (score 0.8575) — an in-silico prediction, not a clinical call.

STS p.Asp503Glu

c.1509T>G · VCV3450909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8575 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8575	likely pathogenic
REVEL	0.751	pathogenic-leaning
SaProt	LLR -10.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP 0.73, phastCons 0.024
Regional constraint	o/e 1.16	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	16.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 D508E vs ClinVar D503E) — 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.Asp503Glu
Coding: c.1509T>G
MANE Select: NM_001320752
Type: single nucleotide variant
Location: chrX:7350033 (GRCh38)
Structure: AlphaFold pLDDT 94.31 · 2 PDB

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.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
STS p.Arg233Pro 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-asp503glu (accessed [today's date]).

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