Is EIF2B2 p.Thr77Pro (c.229A>C) pathogenic?

EIF2B2 p.Thr77Pro (c.229A>C) is classified Uncertain significance in EIF2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.2164); Absent from gnomAD v4.1.

How common is EIF2B2 p.Thr77Pro (c.229A>C) in the general population?

EIF2B2 p.Thr77Pro (c.229A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF2B2 p.Thr77Pro (c.229A>C)?

AlphaMissense predicts likely benign (score 0.2164) — an in-silico prediction, not a clinical call.

EIF2B2 p.Thr77Pro

c.229A>C · rs1889569694 · VCV2085316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2164	likely benign
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -11.16	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,194 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	29.3	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

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: EIF2B2
Protein: p.Thr77Pro
Coding: c.229A>C
MANE Select: NM_014239
dbSNP: rs1889569694
Type: single nucleotide variant
Location: chr14:75003340 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.82 · 38 PDB
Residue 77: an α-helix

Full EIF2B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF2B2 p.Thr77Ala Uncertain significance ★★ ⚠ same residue
EIF2B2 p.Thr77= Likely benign ★ same residue
EIF2B2 c.285-1G>A Likely pathogenic ★★ same type
EIF2B2 c.832-2A>G Likely pathogenic ★★ same type
EIF2B2 p.Arg172Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Glu213Gly Pathogenic ★★ ⚠ same type
EIF2B2 p.Glu304Ter Pathogenic/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/eif2b2-p-thr77pro (accessed [today's date]).

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