Is ETV4 p.Pro115Ser (c.343C>T) pathogenic?

ETV4 p.Pro115Ser (c.343C>T) is classified Likely benign in ETV4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-22). AlphaMissense: likely benign (0.0662); Rare (popmax 0.315%, afr).

How common is ETV4 p.Pro115Ser (c.343C>T) in the general population?

ETV4 p.Pro115Ser (c.343C>T) is rare (popmax 0.315%, afr) (gnomAD).

What do computational predictors say about ETV4 p.Pro115Ser (c.343C>T)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

ETV4 p.Pro115Ser

c.343C>T · rs151095895 · VCV732873

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 17 kb · p 0.059 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.315% African / African-American · 232/73,558 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.0194% 309/1,596,752 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.315%	317
Admixed American	0.0533%	1,876
Middle Eastern	0.0504%	1,985
Remaining individualsnot grpmax-eligible	0.0291%	3,432
European (non-Finnish)	0.00222%	45,147

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: ETV4
Protein: p.Pro115Ser
Coding: c.343C>T
MANE Select: NM_004941 · reported on NM_001079675
dbSNP: rs151095895
Type: single nucleotide variant
Location: chr17:43533899 (GRCh38)

Full ETV4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/etv4-p-pro115ser (accessed [today's date]).

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