Is EEF1D p.Val615Met (c.1843G>A) pathogenic?

EEF1D p.Val615Met (c.1843G>A) is classified Uncertain significance in EEF1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.9891); Ultra-rare (popmax 0.02%, afr).

How common is EEF1D p.Val615Met (c.1843G>A) in the general population?

EEF1D p.Val615Met (c.1843G>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about EEF1D p.Val615Met (c.1843G>A)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

EEF1D p.Val615Met

c.1843G>A · VCV3843471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9891	likely pathogenic
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -14.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.79 · regional, not allelic
Overall
CADD	29.3	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V249M vs ClinVar V615M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,940 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00118% 19/1,613,966 alleles · ultra-rare exomes 9/1,461,740 · genomes 10/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,996
European (non-Finnish)	0.000339%	295,006

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: EEF1D
Protein: p.Val615Met
Coding: c.1843G>A
MANE Select: NM_001130053
Type: single nucleotide variant
Location: chr8:143580074 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 4 PDB
Residue 249 UniProt numbering: the 'catalytic (gef)' region; a β-strand; a UniProt-annotated variant site (in nedtchal; likely pathogenic)

Full EEF1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1D c.1905+1G>A Uncertain significance ★★ same type
EEF1D p.Arg585Cys Uncertain significance ★★ ⚠ same type
EEF1D p.Asp100Gly Uncertain significance ★★ same type
EEF1D p.Asp386Asn Uncertain significance ★★ ⚠ same type
EEF1D p.Gly351Ala Uncertain significance ★★ same type
EEF1D p.Pro350Leu Uncertain significance ★★ same type
EEF1D p.Ser213Asn Uncertain significance ★★ same type
EEF1D p.Thr575Met Uncertain significance ★★ ⚠ 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/eef1d-p-val615met (accessed [today's date]).

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