Is EEF1A1 p.Arg321His (c.962G>A) pathogenic?

EEF1A1 p.Arg321His (c.962G>A) is classified Uncertain significance in EEF1A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely pathogenic (0.8351); Ultra-rare (popmax 0.045%, amr).

How common is EEF1A1 p.Arg321His (c.962G>A) in the general population?

EEF1A1 p.Arg321His (c.962G>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about EEF1A1 p.Arg321His (c.962G>A)?

AlphaMissense predicts likely pathogenic (score 0.8351) — an in-silico prediction, not a clinical call.

EEF1A1 p.Arg321His

c.962G>A · rs781437801 · VCV3087238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8351 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8351	likely pathogenic
REVEL	0.379	indeterminate
SaProt	LLR -13.21	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 -0.009	GERP 0.51, phastCons 0.001
Regional constraint	o/e 0.28	constrained · MANE · 925 bp · p 7e-34 · regional, not allelic
Overall
CADD	23.3	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 0.045% Admixed American · 27/59,992 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00236% 38/1,613,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,222
European (non-Finnish)	0.000932%	107,270

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: EEF1A1
Protein: p.Arg321His
Coding: c.962G>A
MANE Select: NM_001402
dbSNP: rs781437801
Type: single nucleotide variant
Location: chr6:73518421 (GRCh38)
Gene constraint: LOEUF 0.126 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.06 · 14 PDB

Full EEF1A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MTO1 p.Gln595= Benign/Likely benign ★★ same type
EEF1A1 p.Ala448Ser Uncertain significance ★ ⚠ same type
EEF1A1 p.Arg96Thr Uncertain significance ★ ⚠ same type
EEF1A1 p.Asn331His Uncertain significance ★ ⚠ same type
EEF1A1 p.Asp389Asn Uncertain significance ★ ⚠ same type
EEF1A1 p.Cys31Trp Uncertain significance ★ ⚠ same type
EEF1A1 p.Gly151Ser Uncertain significance ★ ⚠ same type
EEF1A1 p.Ile235Val 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/eef1a1-p-arg321his (accessed [today's date]).

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