Is EFTUD2 p.Val97Ala (c.290T>C) pathogenic?

EFTUD2 p.Val97Ala (c.290T>C) is classified Conflicting classifications of pathogenicity in EFTUD2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-03). AlphaMissense: likely benign (0.2966); Very rare (popmax 0.00432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EFTUD2 p.Val97Ala (c.290T>C)?

EFTUD2 p.Val97Ala (c.290T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EFTUD2 p.Val97Ala (c.290T>C) in the general population?

EFTUD2 p.Val97Ala (c.290T>C) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about EFTUD2 p.Val97Ala (c.290T>C)?

AlphaMissense predicts likely benign (score 0.2966) — an in-silico prediction, not a clinical call.

EFTUD2 p.Val97Ala

c.290T>C · rs141916105 · VCV1189532

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2966	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -11.50	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,230 bp · p 0.27 · regional, not allelic
Overall
CADD	24.9	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 0.00432% European (non-Finnish) · 51/1,179,796 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00335% 54/1,613,742 alleles · very rare exomes 53/1,461,616 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,133
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00134%	74,888
South Asian	0.0011%	91,076

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: EFTUD2
Protein: p.Val97Ala
Coding: c.290T>C
MANE Select: NM_004247
dbSNP: rs141916105
Type: single nucleotide variant
Location: chr17:44885316 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 97: an α-helix

Full EFTUD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFTUD2 c.1058+1G>A Pathogenic ★★ same condition
EFTUD2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 p.Arg354Ter Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.2347+3A>G Uncertain significance ★★ same condition
EFTUD2 p.Arg495Gln Uncertain significance ★★ ⚠ same condition
EFTUD2 p.Arg529Cys Uncertain significance ★★ ⚠ same condition
EFTUD2 p.Asn125Asp Uncertain significance ★★ ⚠ same condition
EFTUD2 p.Asn548Ser Uncertain significance ★★ ⚠ 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/eftud2-p-val97ala (accessed [today's date]).

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