Is EEF1G p.Pro385Leu (c.1154C>T) pathogenic?

EEF1G p.Pro385Leu (c.1154C>T) is classified Uncertain significance in EEF1G (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.1076); Ultra-rare (popmax 0.033%, mid).

How common is EEF1G p.Pro385Leu (c.1154C>T) in the general population?

EEF1G p.Pro385Leu (c.1154C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about EEF1G p.Pro385Leu (c.1154C>T)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

EEF1G p.Pro385Leu

c.1154C>T · rs377564786 · VCV2465542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 7,832 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00836%

Overall 0.00868% 140/1,613,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.012%	8,322
European (non-Finnish)	0.0104%	9,593
Remaining individualsnot grpmax-eligible	0.0048%	20,821
South Asian	0.00329%	30,356

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.Pro385Leu
Coding: c.1154C>T
MANE Select: NM_001404
dbSNP: rs377564786
Type: single nucleotide variant
Location: chr11:62560070 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 3 PDB
Residue 385: the ef-1-gamma c-terminal domain; an α-helix

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.Ala2Val Uncertain significance ★ ⚠ same type
EEF1G p.Ala34Thr 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-pro385leu (accessed [today's date]).

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