Is EIF4A2 p.Asp37Val (c.110A>T) pathogenic?

EIF4A2 p.Asp37Val (c.110A>T) is classified Uncertain significance in EIF4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely pathogenic (0.6589); Very rare (popmax 8.47e-05%, nfe).

How common is EIF4A2 p.Asp37Val (c.110A>T) in the general population?

EIF4A2 p.Asp37Val (c.110A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EIF4A2 p.Asp37Val (c.110A>T)?

AlphaMissense predicts likely pathogenic (score 0.6589) — an in-silico prediction, not a clinical call.

EIF4A2 p.Asp37Val

c.110A>T · VCV3899558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6589	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -12.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 3,070 bp · p 3.3e-38 · regional, not allelic
Overall
CADD	33.0	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 0.000657% 1/152,214 alleles · very rare

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: EIF4A2
Protein: p.Asp37Val
Coding: c.110A>T
MANE Select: NM_001967
Type: single nucleotide variant
Location: chr3:186784598 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB
Residue 37: a UniProt-annotated variant site (in nedhss; uncertain significance); an α-helix

Full EIF4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4A2 p.Asp37del Likely pathogenic same residue
EIF4A2 p.Gly362Ser Pathogenic ★★ same type
EIF4A2 p.Ile278Thr Uncertain significance ★★ ⚠ same type
EIF4A2 c.517+1G>T Likely pathogenic ★ same type
EIF4A2 p.Asp338Tyr Likely pathogenic ★ same type
EIF4A2 p.Gly161Arg Likely pathogenic ★ same type
EIF4A2 p.Gly161Trp Likely pathogenic ★ same type
EIF4A2 p.Thr216Ala Pathogenic ★ 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/eif4a2-p-asp37val (accessed [today's date]).

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