Is EEF2K p.Ala558Thr (c.1672G>A) pathogenic?

EEF2K p.Ala558Thr (c.1672G>A) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely pathogenic (0.6841); Very rare (popmax 0.00223%, eas).

How common is EEF2K p.Ala558Thr (c.1672G>A) in the general population?

EEF2K p.Ala558Thr (c.1672G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about EEF2K p.Ala558Thr (c.1672G>A)?

AlphaMissense predicts likely pathogenic (score 0.6841) — an in-silico prediction, not a clinical call.

EEF2K p.Ala558Thr

c.1672G>A · VCV3506790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6841	likely pathogenic
REVEL	0.475	indeterminate
SaProt	LLR -14.71	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	28.1	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

Grpmax group 0.00223% East Asian · 1/44,898 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000248% 4/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,898
South Asian	0.0022%	45,544
European (non-Finnish)	8.47e-05%	1,180,044

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: EEF2K
Protein: p.Ala558Thr
Coding: c.1672G>A
MANE Select: NM_013302
Type: single nucleotide variant
Location: chr16:22266784 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB
Residue 558: an α-helix

Full EEF2K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF2K p.Ala158Asp Uncertain significance ★ ⚠ same type
EEF2K p.Ala164Thr Uncertain significance ★ ⚠ same type
EEF2K p.Ala169Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala306Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala313Asp Uncertain significance ★ ⚠ same type
EEF2K p.Ala617Val Uncertain significance ★ ⚠ same type
EEF2K p.Ala644Thr Uncertain significance ★ ⚠ same type
EEF2K p.Ala76Val 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/eef2k-p-ala558thr (accessed [today's date]).

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