Is EIF6 p.Ile53Val (c.157A>G) pathogenic?

EIF6 p.Ile53Val (c.157A>G) is classified Uncertain significance in EIF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-21). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.00502%, amr).

How common is EIF6 p.Ile53Val (c.157A>G) in the general population?

EIF6 p.Ile53Val (c.157A>G) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about EIF6 p.Ile53Val (c.157A>G)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

EIF6 p.Ile53Val

c.157A>G · rs754663629 · VCV2349388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,287 bp · p 9.4e-05 · regional, not allelic
Overall
CADD	24.2	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 0.00502% Admixed American · 3/59,734 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00293% 47/1,601,584 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,911
European (non-Finnish)	0.00341%	29,312
Remaining individualsnot grpmax-eligible	0.00323%	30,996
African / African-American	0.00134%	74,724
South Asian	0.0011%	90,876

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: EIF6
Protein: p.Ile53Val
Coding: c.157A>G
MANE Select: NM_002212
dbSNP: rs754663629
Type: single nucleotide variant
Location: chr20:35284212 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 91.12 · 48 PDB
Residue 53: a β-strand

Full EIF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF6 p.Ala183Thr Uncertain significance ★ ⚠ same type
EIF6 p.Arg100Gln Uncertain significance ★ ⚠ same type
EIF6 p.Arg85Cys Uncertain significance ★ ⚠ same type
EIF6 p.Arg85His Uncertain significance ★ ⚠ same type
EIF6 p.Asn156Ser Uncertain significance ★ ⚠ same type
EIF6 p.Asn9Thr Uncertain significance ★ ⚠ same type
EIF6 p.Asp144Asn Uncertain significance ★ ⚠ same type
EIF6 p.Asp78Asn 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/eif6-p-ile53val (accessed [today's date]).

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