Is EIF4E1B p.His170Pro (c.509A>C) pathogenic?

EIF4E1B p.His170Pro (c.509A>C) is classified Uncertain significance in EIF4E1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.2221); Ultra-rare (popmax 0.0791%, afr).

How common is EIF4E1B p.His170Pro (c.509A>C) in the general population?

EIF4E1B p.His170Pro (c.509A>C) is ultra-rare (popmax 0.0791%, afr) (gnomAD).

What do computational predictors say about EIF4E1B p.His170Pro (c.509A>C)?

AlphaMissense predicts likely benign (score 0.2221) — an in-silico prediction, not a clinical call.

EIF4E1B p.His170Pro

c.509A>C · rs202006112 · VCV2363268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2221 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0791%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2221	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -10.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 0.66
Regional constraint	o/e 0.93	unconstrained · MANE · 3,189 bp · p 0.22 · regional, not allelic
Overall
CADD	21.8	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 0.0791% African / African-American · 57/72,082 alleles

Filtering AF 0.0626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0568%

Overall 0.00374% 57/1,522,714 alleles · ultra-rare

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: EIF4E1B
Protein: p.His170Pro
Coding: c.509A>C
MANE Select: NM_001099408
dbSNP: rs202006112
Type: single nucleotide variant
Location: chr5:176645411 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.43

Full EIF4E1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4E1B p.Ala195Val Uncertain significance ★ ⚠ same type
EIF4E1B p.Ala226Val Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg134Trp Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg147Ser Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg153Trp Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg172Gly Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg193Gly Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg193Ser 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/eif4e1b-p-his170pro (accessed [today's date]).

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