Is EIF2B5 p.Val201Met (c.601G>A) pathogenic?

EIF2B5 p.Val201Met (c.601G>A) is classified Uncertain significance in EIF2B5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-27). AlphaMissense: likely benign (0.1301); Very rare (popmax 0.0089%, nfe).

How common is EIF2B5 p.Val201Met (c.601G>A) in the general population?

EIF2B5 p.Val201Met (c.601G>A) is very rare (popmax 0.0089%, nfe) (gnomAD).

What do computational predictors say about EIF2B5 p.Val201Met (c.601G>A)?

AlphaMissense predicts likely benign (score 0.1301) — an in-silico prediction, not a clinical call.

EIF2B5 p.Val201Met

c.601G>A · rs574694961 · VCV2174931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1301 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1301	likely benign
REVEL	0.282	benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Pangolin	Δ0.33	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.46	GERP -3.4, phastCons 0.019
Regional constraint	o/e 0.84	unconstrained · MANE · 8,264 bp · p 4.1e-06 · regional, not allelic
Overall
CADD	19.8	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 0.0089% European (non-Finnish) · 105/1,180,056 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00663% 107/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,239
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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: EIF2B5
Protein: p.Val201Met
Coding: c.601G>A
MANE Select: NM_003907
dbSNP: rs574694961
Type: single nucleotide variant
Location: chr3:184137992 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 37 PDB
Residue 201: a β-strand

Full EIF2B5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF2B5 p.Val201= Likely benign ★ same residue
EIF2B5 p.Ala403Val Pathogenic/Likely pathogenic ★★ ⚠ same type
EIF2B5 p.Arg113Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
EIF2B5 p.Arg113His Pathogenic ★★ ⚠ same type
EIF2B5 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B5 p.Arg136Cys Pathogenic/Likely pathogenic ★★ same type
EIF2B5 p.Arg136His Pathogenic ★★ same type
EIF2B5 p.Arg195Cys Likely pathogenic ★★ ⚠ 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/eif2b5-p-val201met (accessed [today's date]).

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