Is EIF2B2 p.Phe288Ser (c.863T>C) pathogenic?

EIF2B2 p.Phe288Ser (c.863T>C) is classified Uncertain significance in EIF2B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely pathogenic (0.738); Very rare (popmax 0.00133%, afr).

How common is EIF2B2 p.Phe288Ser (c.863T>C) in the general population?

EIF2B2 p.Phe288Ser (c.863T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about EIF2B2 p.Phe288Ser (c.863T>C)?

AlphaMissense predicts likely pathogenic (score 0.738) — an in-silico prediction, not a clinical call.

EIF2B2 p.Phe288Ser

c.863T>C · rs376944725 · VCV2039076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.738	likely pathogenic
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,194 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	27.7	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 0.00133% African / African-American · 1/75,062 alleles

Overall 0.000124% 2/1,614,050 alleles · very rare exomes 2/1,461,692 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,062
European (non-Finnish)	8.47e-05%	1,179,967

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: EIF2B2
Protein: p.Phe288Ser
Coding: c.863T>C
MANE Select: NM_014239
dbSNP: rs376944725
Type: single nucleotide variant
Location: chr14:75007753 (GRCh38)
Gene constraint: LOEUF 1.25 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.82 · 38 PDB

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

Similar variants

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
EIF2B2 p.Gly200Val Pathogenic/Likely pathogenic ★★ same type
EIF2B2 p.Lys273Arg 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-phe288ser (accessed [today's date]).

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