Is EEF1G p.Ala2Val (c.5C>T) pathogenic?

EEF1G p.Ala2Val (c.5C>T) is classified Uncertain significance in EEF1G (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: ambiguous (0.414); Very rare (popmax 0.0011%, sas).

How common is EEF1G p.Ala2Val (c.5C>T) in the general population?

EEF1G p.Ala2Val (c.5C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EEF1G p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.414) — an in-silico prediction, not a clinical call.

EEF1G p.Ala2Val

c.5C>T · VCV3843485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.414	ambiguous
REVEL	0.07	moderately benign-leaning
SaProt	LLR -2.19	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,963 bp · p 0.0074 · regional, not allelic
Overall
CADD	26.6	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 0.0011% South Asian · 1/91,070 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,430 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,070
European (non-Finnish)	0.000339%	294,960

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: EEF1G
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_001404
Type: single nucleotide variant
Location: chr11:62573838 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 3 PDB
Residue 2: the gst n-terminal domain; a modified residue (n-acetylalanine)

Full EEF1G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1G p.Ala183Asp Uncertain significance ★ ⚠ same type
EEF1G p.Ala183Ser Uncertain significance ★ ⚠ same type
EEF1G p.Ala202Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala254Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala269Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala281Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala34Thr Uncertain significance ★ ⚠ same type
EEF1G p.Ala429Gly 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/eef1g-p-ala2val (accessed [today's date]).

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