Is EEF2K p.Arg448Gln (c.1343G>A) pathogenic?

EEF2K p.Arg448Gln (c.1343G>A) is classified Uncertain significance in EEF2K (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-26). AlphaMissense: likely benign (0.1114); Ultra-rare (popmax 0.0223%, eas).

How common is EEF2K p.Arg448Gln (c.1343G>A) in the general population?

EEF2K p.Arg448Gln (c.1343G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about EEF2K p.Arg448Gln (c.1343G>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

EEF2K p.Arg448Gln

c.1343G>A · rs751431906 · VCV2298000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Pangolin	Δ0.22	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 0.36, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 58 kb · p 0.22 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0223% East Asian · 10/44,810 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00918%

Overall 0.00124% 20/1,612,470 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,481
Remaining individualsnot grpmax-eligible	0.00321%	31,183
South Asian	0.0022%	45,442
Admixed American	0.00167%	59,844
African / African-American	0.00134%	74,854
European (non-Finnish)	0.000339%	294,809

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.Arg448Gln
Coding: c.1343G>A
MANE Select: NM_013302
dbSNP: rs751431906
Type: single nucleotide variant
Location: chr16:22263153 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36 · 10 PDB
Residue 448: the 'disordered' region

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

Similar variants

EEF2K p.Arg448Gly Uncertain significance ★ ⚠ same residue
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.Ala558Thr Uncertain significance ★ ⚠ same type
EEF2K p.Ala617Val 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-arg448gln (accessed [today's date]).

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