Is EIF6 p.His162Pro (c.485A>C) pathogenic?

EIF6 p.His162Pro (c.485A>C) is classified Uncertain significance in EIF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.6941); Absent from gnomAD v4.1.

How common is EIF6 p.His162Pro (c.485A>C) in the general population?

EIF6 p.His162Pro (c.485A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF6 p.His162Pro (c.485A>C)?

AlphaMissense predicts likely pathogenic (score 0.6941) — an in-silico prediction, not a clinical call.

EIF6 p.His162Pro

c.485A>C · VCV4663748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6941	likely pathogenic
REVEL	0.963	strongly pathogenic-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,287 bp · p 9.4e-05 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EIF6
Protein: p.His162Pro
Coding: c.485A>C
MANE Select: NM_002212
Type: single nucleotide variant
Location: chr20:35280003 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 91.12 · 48 PDB

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-his162pro (accessed [today's date]).

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