Is EIF4E1B p.Arg67Ser (c.201G>T) pathogenic?

EIF4E1B p.Arg67Ser (c.201G>T) is classified Uncertain significance in EIF4E1B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.3009); Ultra-rare (popmax 0.0561%, eas).

How common is EIF4E1B p.Arg67Ser (c.201G>T) in the general population?

EIF4E1B p.Arg67Ser (c.201G>T) is ultra-rare (popmax 0.0561%, eas) (gnomAD).

What do computational predictors say about EIF4E1B p.Arg67Ser (c.201G>T)?

AlphaMissense predicts likely benign (score 0.3009) — an in-silico prediction, not a clinical call.

EIF4E1B p.Arg67Ser

c.201G>T · rs750550082 · VCV2209829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3009 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3009	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.45	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.28 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP -0.42, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,189 bp · p 0.22 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% East Asian · 25/44,568 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0332%

Overall 0.00168% 27/1,604,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0561%	1,783
Remaining individualsnot grpmax-eligible	0.00322%	31,070

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.Arg67Ser
Coding: c.201G>T
MANE Select: NM_001099408
dbSNP: rs750550082
Type: single nucleotide variant
Location: chr5:176643639 (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-arg67ser (accessed [today's date]).

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