Is ERI1 p.Asp298Ala (c.893A>C) pathogenic?

ERI1 p.Asp298Ala (c.893A>C) is classified Pathogenic in ERI1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely pathogenic (0.9992); Very rare (popmax 0.000169%, nfe); Associated with spondyloepimetaphyseal dysplasia, Guo-Campeau type.

What condition is associated with ERI1 p.Asp298Ala (c.893A>C)?

ERI1 p.Asp298Ala (c.893A>C) is associated with spondyloepimetaphyseal dysplasia, Guo-Campeau type (ClinVar).

How common is ERI1 p.Asp298Ala (c.893A>C) in the general population?

ERI1 p.Asp298Ala (c.893A>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ERI1 p.Asp298Ala (c.893A>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

ERI1 p.Asp298Ala

c.893A>C · rs1433280953 · VCV2674627

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondyloepimetaphyseal dysplasia, Guo-Campeau type

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar · top 1% in ERI1
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -13.97	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 27 kb · p 9.3e-16 · regional, not allelic
Overall
CADD	29.6	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 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,884 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.Asp298Ala
Coding: c.893A>C
MANE Select: NM_153332
dbSNP: rs1433280953
Type: single nucleotide variant
Location: chr8:9029877 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 298: a binding site; a UniProt-annotated variant site (in semdgc; likely pathogenic); a UniProt-annotated variant site (in hxal; likely pathogenic); a UniProt-annotated variant site (in semdgc; likely pathogenic; inhibits 3'-end histone mrna exonuclease activity); a UniProt-annotated variant site (in semdgc; likely pathogenic; loss-of-function variant unable to rescue defective maturation of 5.8s rrna in eri1-deficient cells); the exonuclease domain; an α-helix

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

Disease context

spondyloepimetaphyseal dysplasia, Guo-Campeau type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERI1 p.Asp298Gly Likely pathogenic ★ same residue
ERI1 p.Arg304Ter Likely pathogenic ★ same condition
ERI1 p.Asp134Gly Likely pathogenic ★ same condition
ERI1 p.Glu150Asp Likely pathogenic ★ same condition
ERI1 p.Pro155Leu Likely pathogenic ★ same condition
ERI1 p.Ser21Ter Likely pathogenic ★ same condition
ERI1 p.Ser299Pro Likely pathogenic ★ same condition
ERI1 p.Ser333Tyr 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/eri1-p-asp298ala (accessed [today's date]).

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