Is ETS1 p.Ala337Ser (c.1009G>T) pathogenic?

ETS1 p.Ala337Ser (c.1009G>T) is classified Uncertain significance in ETS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0775); Absent from gnomAD v4.1.

How common is ETS1 p.Ala337Ser (c.1009G>T) in the general population?

ETS1 p.Ala337Ser (c.1009G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ETS1 p.Ala337Ser (c.1009G>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

ETS1 p.Ala337Ser

c.1009G>T · VCV4251341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.74	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 1.1	GERP 0.45, phastCons 0.52
Regional constraint	o/e 0.91	unconstrained · MANE · 4,716 bp · p 0.29 · regional, not allelic
Overall
CADD	14.99	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 A293S vs ClinVar A337S) — 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: ETS1
Protein: p.Ala337Ser
Coding: c.1009G>T
MANE Select: NM_001143820
Type: single nucleotide variant
Location: chr11:128480305 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.95 · 21 PDB

Full ETS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ETS1 c.*1736A>G Benign ★★ same type
ETS1 p.Ala151Thr Likely benign ★★ same type
ETS1 p.Arg307= Benign ★★ same type
ETS1 p.Pro12= Benign ★★ same type
ETS1 p.Ser200= Benign ★★ same type
ETS1 p.Arg35Ter Likely pathogenic ★ same type
ETS1 p.Ala338Val Uncertain significance ★ ⚠ same type
ETS1 p.Ala475Thr Uncertain significance ★ ⚠ 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/ets1-p-ala337ser (accessed [today's date]).

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