Is EFTUD2 p.Lys681Arg (c.2042A>G) pathogenic?

EFTUD2 p.Lys681Arg (c.2042A>G) is classified Conflicting classifications of pathogenicity in EFTUD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-28). AlphaMissense: likely benign (0.0929); Very rare (popmax 0.00559%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EFTUD2 p.Lys681Arg (c.2042A>G)?

EFTUD2 p.Lys681Arg (c.2042A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EFTUD2 p.Lys681Arg (c.2042A>G) in the general population?

EFTUD2 p.Lys681Arg (c.2042A>G) is very rare (popmax 0.00559%, nfe) (gnomAD).

What do computational predictors say about EFTUD2 p.Lys681Arg (c.2042A>G)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

EFTUD2 p.Lys681Arg

c.2042A>G · rs144798973 · VCV1380201

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -9.12	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 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	23.8	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 0.00559% European (non-Finnish) · 66/1,179,664 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00428% 69/1,613,736 alleles · very rare exomes 60/1,461,454 · genomes 9/152,282 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00559%	17,874
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00133%	75,030

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.Lys681Arg
Coding: c.2042A>G
MANE Select: NM_004247
dbSNP: rs144798973
Type: single nucleotide variant
Location: chr17:44857078 (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.Lys681Glu Uncertain significance ★ ⚠ 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-lys681arg (accessed [today's date]).

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