Is EIF4EBP2 p.Pro71Leu (c.212C>T) pathogenic?

EIF4EBP2 p.Pro71Leu (c.212C>T) is classified Uncertain significance in EIF4EBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely pathogenic (0.9931); Very rare (popmax 0.00335%, amr).

How common is EIF4EBP2 p.Pro71Leu (c.212C>T) in the general population?

EIF4EBP2 p.Pro71Leu (c.212C>T) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about EIF4EBP2 p.Pro71Leu (c.212C>T)?

AlphaMissense predicts likely pathogenic (score 0.9931) — an in-silico prediction, not a clinical call.

EIF4EBP2 p.Pro71Leu

c.212C>T · rs772761413 · VCV2230513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9931	likely pathogenic
REVEL	0.552	indeterminate
SaProt	LLR -12.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 17 kb · p 0.043 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00335% Admixed American · 2/59,786 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000411% 6/1,460,632 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,893
European (non-Finnish)	0.000339%	294,902

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: EIF4EBP2
Protein: p.Pro71Leu
Coding: c.212C>T
MANE Select: NM_004096
dbSNP: rs772761413
Type: single nucleotide variant
Location: chr10:70419980 (GRCh38)
Gene constraint: LOEUF 1.607 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 75.93 · 2 PDB
Residue 71: the 'disordered' region

Full EIF4EBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4EBP2 p.Gly6Asp Likely benign ★★ ⚠ same type
EIF4EBP2 p.Ala23Thr Uncertain significance ★ ⚠ same type
EIF4EBP2 p.Asn102Lys Uncertain significance ★ ⚠ same type
EIF4EBP2 p.Asn103Ser Uncertain significance ★ ⚠ same type
EIF4EBP2 p.Asp105His Uncertain significance ★ ⚠ same type
EIF4EBP2 p.His104Gln Uncertain significance ★ ⚠ same type
EIF4EBP2 p.His108Tyr Uncertain significance ★ ⚠ same type
EIF4EBP2 p.His32Pro 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/eif4ebp2-p-pro71leu (accessed [today's date]).

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