Is EEF2KMT p.Ile245Ser (c.734T>G) pathogenic?

EEF2KMT p.Ile245Ser (c.734T>G) is classified Uncertain significance in EEF2KMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely pathogenic (0.8516); Absent from gnomAD v4.1.

How common is EEF2KMT p.Ile245Ser (c.734T>G) in the general population?

EEF2KMT p.Ile245Ser (c.734T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEF2KMT p.Ile245Ser (c.734T>G)?

AlphaMissense predicts likely pathogenic (score 0.8516) — an in-silico prediction, not a clinical call.

EEF2KMT p.Ile245Ser

c.734T>G · VCV4663141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8516 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8516	likely pathogenic · top 6% in EEF2KMT
REVEL	0.556	indeterminate
SaProt	LLR -14.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 12 kb · p 0.0037 · regional, not allelic
Overall
CADD	25.6	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: EEF2KMT
Protein: p.Ile245Ser
Coding: c.734T>G
MANE Select: NM_201400
Type: single nucleotide variant
Location: chr16:5090092 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 245: a β-strand

Full EEF2KMT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG1 p.Arg438Trp Pathogenic ★★ ⚠ same type
ALG1 c.1264-11T>G Uncertain significance ★★ same type
ALG1 p.Arg448Gln Uncertain significance ★★ ⚠ same type
ALG1 p.Asp450Asn Uncertain significance ★★ ⚠ same type
ALG1 p.Asp450Gly Uncertain significance ★★ ⚠ same type
ALG1 p.Asp463Tyr Uncertain significance ★★ ⚠ same type
ALG1 p.Lys439Arg Uncertain significance ★★ ⚠ same type
ALG1 p.Pro430Thr 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/eef2kmt-p-ile245ser (accessed [today's date]).

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