Is EIF3A p.Tyr697Cys (c.2090A>G) pathogenic?

EIF3A p.Tyr697Cys (c.2090A>G) is classified Uncertain significance in EIF3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.9738); Absent from gnomAD v4.1.

How common is EIF3A p.Tyr697Cys (c.2090A>G) in the general population?

EIF3A p.Tyr697Cys (c.2090A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF3A p.Tyr697Cys (c.2090A>G)?

AlphaMissense predicts likely pathogenic (score 0.9738) — an in-silico prediction, not a clinical call.

EIF3A p.Tyr697Cys

c.2090A>G · rs1564754055 · VCV3087917

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9738	likely pathogenic
REVEL	0.527	indeterminate
SaProt	LLR -13.53	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 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,500 bp · p 9.2e-15 · regional, not allelic
Overall
CADD	25.8	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: EIF3A
Protein: p.Tyr697Cys
Coding: c.2090A>G
MANE Select: NM_003750
dbSNP: rs1564754055
Type: single nucleotide variant
Location: chr10:119056846 (GRCh38)
Gene constraint: LOEUF 0.18 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 30 PDB
Residue 697: an α-helix; the 'interaction with eif3b' region

Full EIF3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF3A p.Ala1358= Benign ★★ same type
EIF3A p.Arg1046Trp Likely benign ★★ ⚠ same type
EIF3A p.Arg406= Benign/Likely benign ★★ same type
EIF3A p.Arg803Lys Benign ★★ ⚠ same type
EIF3A p.Asp993Glu Benign ★★ same type
EIF3A p.Arg1273Ser Likely pathogenic ★ ⚠ same type
EIF3A p.Ala1354Ser Uncertain significance ★ ⚠ same type
EIF3A p.Ala181Gly 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/eif3a-p-tyr697cys (accessed [today's date]).

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