Is EIF4E1B p.Ala195Val (c.584C>T) pathogenic?

EIF4E1B p.Ala195Val (c.584C>T) is classified Uncertain significance in EIF4E1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.2736); Very rare (popmax 0.00838%, nfe).

How common is EIF4E1B p.Ala195Val (c.584C>T) in the general population?

EIF4E1B p.Ala195Val (c.584C>T) is very rare (popmax 0.00838%, nfe) (gnomAD).

What do computational predictors say about EIF4E1B p.Ala195Val (c.584C>T)?

AlphaMissense predicts likely benign (score 0.2736) — an in-silico prediction, not a clinical call.

EIF4E1B p.Ala195Val

c.584C>T · rs1296660855 · VCV2407157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00838%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2736	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP -2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,189 bp · p 0.22 · regional, not allelic
Overall
CADD	25.7	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 0.00838% European (non-Finnish) · 95/1,133,022 alleles

Filtering AF 0.007% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0065%

Overall 0.00641% 97/1,513,296 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00838%	11,927
East Asian	0.00232%	43,088
Finnishnot grpmax-eligible	0.00164%	61,102

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.Ala195Val
Coding: c.584C>T
MANE Select: NM_001099408
dbSNP: rs1296660855
Type: single nucleotide variant
Location: chr5:176645486 (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.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
EIF4E1B p.Arg206Gly 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-ala195val (accessed [today's date]).

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