Is EEF1E1 p.Ala69Ser (c.205G>T) pathogenic?

EEF1E1 p.Ala69Ser (c.205G>T) is classified Uncertain significance in EEF1E1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3915); Very rare (popmax 0.01%, amr).

How common is EEF1E1 p.Ala69Ser (c.205G>T) in the general population?

EEF1E1 p.Ala69Ser (c.205G>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about EEF1E1 p.Ala69Ser (c.205G>T)?

AlphaMissense predicts ambiguous (score 0.3915) — an in-silico prediction, not a clinical call.

EEF1E1 p.Ala69Ser

c.205G>T · VCV4663115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Computational evidence

Protein change
AlphaMissense	0.3915	ambiguous
REVEL	0.335	indeterminate
SaProt	LLR -8.31	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.77 · 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 0.01% Admixed American · 6/60,020 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00136% 22/1,614,154 alleles · very rare exomes 22/1,461,886 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,003
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.00127%	78,668

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: EEF1E1
Protein: p.Ala69Ser
Coding: c.205G>T
MANE Select: NM_004280
Type: single nucleotide variant
Location: chr6:8097350 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.44 · 6 PDB
Residue 69: the gst c-terminal domain; an α-helix; the 'c-terminal' region

Full EEF1E1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1E1 p.Ala5Thr Uncertain significance ★ ⚠ same type
EEF1E1 p.Arg144His Uncertain significance ★ ⚠ same type
EEF1E1 p.Asp90Asn Uncertain significance ★ ⚠ same type
EEF1E1 p.Gln150Leu Uncertain significance ★ ⚠ same type
EEF1E1 p.Glu67Lys Uncertain significance ★ ⚠ same type
EEF1E1 p.Gly19Glu Uncertain significance ★ ⚠ same type
EEF1E1 p.Ile118Thr Uncertain significance ★ ⚠ same type
EEF1E1 p.Ile47Val 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/eef1e1-p-ala69ser (accessed [today's date]).

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