Is EIF2B2 p.Gln44Arg (c.131A>G) pathogenic?

EIF2B2 p.Gln44Arg (c.131A>G) is classified Likely benign in EIF2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.0662); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EIF2B2 p.Gln44Arg (c.131A>G)?

EIF2B2 p.Gln44Arg (c.131A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EIF2B2 p.Gln44Arg (c.131A>G) in the general population?

EIF2B2 p.Gln44Arg (c.131A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF2B2 p.Gln44Arg (c.131A>G)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

EIF2B2 p.Gln44Arg

c.131A>G · rs1889563958 · VCV3087897

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -5.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.25, phastCons 0.99
Regional constraint	o/e 0.81	unconstrained · MANE · 6,194 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	15.0	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.Gln44Arg
Coding: c.131A>G
MANE Select: NM_014239
dbSNP: rs1889563958
Type: single nucleotide variant
Location: chr14:75003121 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.82 · 38 PDB
Residue 44: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EIF2B2 p.Ala195Ser Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Ala6Pro Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Arg43Cys Uncertain significance ★★ ⚠ same condition
EIF2B2 p.His286Arg Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Ile151Thr Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Ile190Met Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Ile222Val Uncertain significance ★★ ⚠ same condition
EIF2B2 p.Lys179Arg Uncertain significance ★★ ⚠ same condition

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-gln44arg (accessed [today's date]).

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