Is EEF1A2 p.Val264Met (c.790G>A) pathogenic?

EEF1A2 p.Val264Met (c.790G>A) is classified Uncertain significance in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely pathogenic (0.9987); Very rare (popmax 8.49e-05%, nfe).

How common is EEF1A2 p.Val264Met (c.790G>A) in the general population?

EEF1A2 p.Val264Met (c.790G>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about EEF1A2 p.Val264Met (c.790G>A)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

EEF1A2 p.Val264Met

c.790G>A · rs2516775531 · VCV1801962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -12.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	28.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,242 alleles

Overall 6.9e-05% 1/1,450,276 alleles · very rare

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: EEF1A2
Protein: p.Val264Met
Coding: c.790G>A
MANE Select: NM_001958
dbSNP: rs2516775531
Type: single nucleotide variant
Location: chr20:63490718 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 264: a β-strand

Full EEF1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1A2 p.Val264= Likely benign ★ same residue
EEF1A2 p.Arg266Gln Likely pathogenic ★★ same type
EEF1A2 p.Arg266Trp Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg423Cys Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg69Cys Pathogenic ★★ same type
EEF1A2 p.Asp252Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
EEF1A2 p.Asp91Asn Pathogenic ★★ ⚠ same type
EEF1A2 p.Asp97Asn Pathogenic/Likely pathogenic ★★ 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/eef1a2-p-val264met (accessed [today's date]).

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