Is EIF2B3 p.Pro143= (c.429C>T) pathogenic?

EIF2B3 p.Pro143= (c.429C>T) is classified Likely benign in EIF2B3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Very rare (popmax 0.00673%, afr).

How common is EIF2B3 p.Pro143= (c.429C>T) in the general population?

EIF2B3 p.Pro143= (c.429C>T) is very rare (popmax 0.00673%, afr) (gnomAD).

EIF2B3 p.Pro143=

c.429C>T · rs748442078 · VCV745667

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00673%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.26	GERP -2.5, phastCons 0.46
Overall
CADD	11.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00673% African / African-American · 5/74,334 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00234%

Overall 0.00405% 65/1,603,058 alleles · very rare exomes 54/1,451,182 · genomes 11/151,876 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0219%	4,561
African / African-Americangrpmax	0.00673%	14,867
East Asian	0.00671%	14,901
European (non-Finnish)	0.00349%	28,666
Remaining individualsnot grpmax-eligible	0.00323%	30,980

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EIF2B3
Protein: p.Pro143=
Coding: c.429C>T
MANE Select: NM_020365
dbSNP: rs748442078
Type: single nucleotide variant
Location: chr1:44941531 (GRCh38)
Gene constraint: LOEUF 0.522 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.51 · 37 PDB

Full EIF2B3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF2B3 p.Ala87Val Pathogenic/Likely pathogenic ★★ same type
EIF2B3 p.Arg225Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
EIF2B3 p.Arg225Trp Likely pathogenic ★★ same type
EIF2B3 p.Ile346Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
EIF2B3 p.Val30Ala Pathogenic/Likely pathogenic ★★ same type
EIF2B3 c.784+4A>C Uncertain significance ★★ same type
EIF2B3 c.*55C>T Uncertain significance ★★ same type
EIF2B3 p.Ala280Thr 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/eif2b3-p-pro143 (accessed [today's date]).

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