Is ETV6 p.Val320Phe (c.958G>T) pathogenic?

ETV6 p.Val320Phe (c.958G>T) is classified Uncertain significance in ETV6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-20). AlphaMissense: likely benign (0.2516); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ETV6 p.Val320Phe (c.958G>T)?

ETV6 p.Val320Phe (c.958G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ETV6 p.Val320Phe (c.958G>T) in the general population?

ETV6 p.Val320Phe (c.958G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ETV6 p.Val320Phe (c.958G>T)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

ETV6 p.Val320Phe

c.958G>T · VCV4618839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,484)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -7.00	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.2 · regional, not allelic
Overall
CADD	25.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,484). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ETV6
Protein: p.Val320Phe
Coding: c.958G>T
MANE Select: NM_001987
Type: single nucleotide variant
Location: chr12:11869918 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.61 · 43 PDB

Full ETV6 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

ETV6 p.Val320Ala Uncertain significance ★ ⚠ same residue
ETV6 p.Val320Ile Uncertain significance ★ ⚠ same residue
ETV6 p.Val320= Likely benign ★ same residue
ETV6 p.Arg359Ter Pathogenic ★★ same condition
ETV6 p.Arg369Gln Pathogenic/Likely pathogenic ★★ same condition
ETV6 c.1010-3T>C Uncertain significance ★★ same condition
ETV6 p.Ala247Gly Uncertain significance ★★ ⚠ same condition
ETV6 p.Ala67Asp 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/etv6-p-val320phe (accessed [today's date]).

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