Is ERI1 p.Cys294Arg (c.880T>C) pathogenic?

ERI1 p.Cys294Arg (c.880T>C) is classified Uncertain significance in ERI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely pathogenic (0.9411); Very rare (popmax 0.00223%, eas).

How common is ERI1 p.Cys294Arg (c.880T>C) in the general population?

ERI1 p.Cys294Arg (c.880T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ERI1 p.Cys294Arg (c.880T>C)?

AlphaMissense predicts likely pathogenic (score 0.9411) — an in-silico prediction, not a clinical call.

ERI1 p.Cys294Arg

c.880T>C · VCV3510078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9411	likely pathogenic
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.95, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 27 kb · p 9.3e-16 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 6.84e-05% 1/1,461,886 alleles · very rare

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: ERI1
Protein: p.Cys294Arg
Coding: c.880T>C
MANE Select: NM_153332
Type: single nucleotide variant
Location: chr8:9029864 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 294: a UniProt-annotated variant site (in semdgc; likely pathogenic); a UniProt-annotated variant site (in hxal; likely pathogenic); the exonuclease domain

Full ERI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERI1 p.Ser333Tyr Uncertain significance ★★ ⚠ same type
ERI1 p.Thr221Ala Uncertain significance ★★ ⚠ same type
ERI1 p.Arg291= Benign ★★ same type
ERI1 p.Arg304Ter Likely pathogenic ★ same type
ERI1 p.Asp134Gly Likely pathogenic ★ same type
ERI1 p.Asp298Gly Likely pathogenic ★ same type
ERI1 p.Gln244Ter Likely pathogenic ★ same type
ERI1 p.Glu150Asp Likely pathogenic ★ 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/eri1-p-cys294arg (accessed [today's date]).

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