Is EFTUD2 p.Val45Ile (c.133G>A) pathogenic?

EFTUD2 p.Val45Ile (c.133G>A) is classified Benign/Likely benign in EFTUD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-05). AlphaMissense: likely benign (0.0648); Rare (popmax 0.276%, afr).

How common is EFTUD2 p.Val45Ile (c.133G>A) in the general population?

EFTUD2 p.Val45Ile (c.133G>A) is rare (popmax 0.276%, afr) (gnomAD).

What do computational predictors say about EFTUD2 p.Val45Ile (c.133G>A)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

EFTUD2 p.Val45Ile

c.133G>A · rs150335245 · VCV259252

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.276%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.7, phastCons 0.25
Regional constraint	o/e 0.90	unconstrained · MANE · 9,230 bp · p 0.27 · regional, not allelic
Overall
CADD	11.66	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 0.276% African / African-American · 207/75,024 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.0182% 293/1,613,914 alleles · rare exomes 175/1,461,626 · genomes 118/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.276%	362
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.0167%	5,999
Middle Eastern	0.0165%	6,048
European (non-Finnish)	0.00254%	39,332
South Asian	0.0011%	91,064

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.Val45Ile
Coding: c.133G>A
MANE Select: NM_004247
dbSNP: rs150335245
Type: single nucleotide variant
Location: chr17:44886723 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 45: the 'disordered' region

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

Similar variants

EFTUD2 c.1058+1G>A Pathogenic ★★ same type
EFTUD2 c.1414-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.1607+1G>T Likely pathogenic ★★ same type
EFTUD2 c.1962+1G>A Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2133-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.2562-2A>G Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.702+1G>T Pathogenic/Likely pathogenic ★★ same type
EFTUD2 c.703-2A>G Pathogenic/Likely 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/eftud2-p-val45ile (accessed [today's date]).

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