Is EEF1A2 p.Asp252Asn (c.754G>A) pathogenic?

EEF1A2 p.Asp252Asn (c.754G>A) is classified Pathogenic/Likely pathogenic in EEF1A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1; Associated with EEF1A2-related disorder.

What condition is associated with EEF1A2 p.Asp252Asn (c.754G>A)?

EEF1A2 p.Asp252Asn (c.754G>A) is associated with EEF1A2-related disorder (ClinVar).

How common is EEF1A2 p.Asp252Asn (c.754G>A) in the general population?

EEF1A2 p.Asp252Asn (c.754G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF1A2 p.Asp252Asn (c.754G>A)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

EEF1A2 p.Asp252Asn

c.754G>A · rs786205865 · VCV2631662

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EEF1A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic ✓ concordant with ClinVar
REVEL	0.273	benign-leaning
SaProt	LLR -13.92	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.60 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 4,822 bp · p 4e-36 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EEF1A2
Protein: p.Asp252Asn
Coding: c.754G>A
MANE Select: NM_001958
dbSNP: rs786205865
Type: single nucleotide variant
Location: chr20:63493155 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 252: a UniProt-annotated variant site (in mrd38); a β-strand

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

Disease context

EEF1A2-related disorder

Similar variants

EEF1A2 p.Asp252Tyr Likely pathogenic ★ same residue
EEF1A2 p.Asp252= Likely benign ★★ same residue
EEF1A2 p.Asp252His Conflicting classifications of pathogenicity ⚠ same residue
EEF1A2 p.Arg266Trp Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Asp97Asn Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Glu122Lys Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Glu124Lys Pathogenic/Likely pathogenic ★★ same condition
EEF1A2 p.Arg382Leu Likely pathogenic ★ same condition

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-asp252asn (accessed [today's date]).

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