Is EEF2 p.Ile485Val (c.1453A>G) pathogenic?

EEF2 p.Ile485Val (c.1453A>G) is classified Conflicting classifications of pathogenicity in EEF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1331); Ultra-rare (popmax 0.0283%, nfe).

How common is EEF2 p.Ile485Val (c.1453A>G) in the general population?

EEF2 p.Ile485Val (c.1453A>G) is ultra-rare (popmax 0.0283%, nfe) (gnomAD).

What do computational predictors say about EEF2 p.Ile485Val (c.1453A>G)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

EEF2 p.Ile485Val

c.1453A>G · rs200110903 · VCV2273439

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.638	indeterminate
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 657 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	24.4	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 0.0283% European (non-Finnish) · 334/1,180,050 alleles

Filtering AF 0.0258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.022% 355/1,613,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0283%	3,533
Middle Eastern	0.0164%	6,084
African / African-American	0.0107%	9,369
Remaining individualsnot grpmax-eligible	0.008%	12,498
East Asian	0.00445%	22,452
South Asian	0.00439%	22,773
Finnishnot grpmax-eligible	0.00157%	63,728

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: EEF2
Protein: p.Ile485Val
Coding: c.1453A>G
MANE Select: NM_001961
dbSNP: rs200110903
Type: single nucleotide variant
Location: chr19:3979960 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.97 · 26 PDB
Residue 485: a β-strand

Full EEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF2 p.Ala237Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala238Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala338Gly Uncertain significance ★★ ⚠ same type
EEF2 p.Ala624Thr Uncertain significance ★★ ⚠ same type
EEF2 p.Ala808Val Uncertain significance ★★ ⚠ same type
EEF2 p.Arg633His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg647His Uncertain significance ★★ ⚠ same type
EEF2 p.Arg726Trp 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/eef2-p-ile485val (accessed [today's date]).

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