Is EFTUD2 p.Lys681Glu (c.2041A>G) pathogenic?

EFTUD2 p.Lys681Glu (c.2041A>G) is classified Uncertain significance in EFTUD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). AlphaMissense: likely pathogenic (0.8765); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EFTUD2 p.Lys681Glu (c.2041A>G)?

EFTUD2 p.Lys681Glu (c.2041A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EFTUD2 p.Lys681Glu (c.2041A>G) in the general population?

EFTUD2 p.Lys681Glu (c.2041A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFTUD2 p.Lys681Glu (c.2041A>G)?

AlphaMissense predicts likely pathogenic (score 0.8765) — an in-silico prediction, not a clinical call.

EFTUD2 p.Lys681Glu

c.2041A>G · VCV4838910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8765 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8765	likely pathogenic
REVEL	0.515	indeterminate
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 5,858 bp · p 6.8e-32 · regional, not allelic
Overall
CADD	29.5	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

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: EFTUD2
Protein: p.Lys681Glu
Coding: c.2041A>G
MANE Select: NM_004247
Type: single nucleotide variant
Location: chr17:44857079 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 681: a β-strand

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 p.Lys681Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-lys681glu (accessed [today's date]).

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