Is ERI2 p.Ala2Val (c.5C>T) pathogenic?

ERI2 p.Ala2Val (c.5C>T) is classified Uncertain significance in ERI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely pathogenic (0.8834); Very rare (popmax 8.71e-05%, nfe).

How common is ERI2 p.Ala2Val (c.5C>T) in the general population?

ERI2 p.Ala2Val (c.5C>T) is very rare (popmax 8.71e-05%, nfe) (gnomAD).

What do computational predictors say about ERI2 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.8834) — an in-silico prediction, not a clinical call.

ERI2 p.Ala2Val

c.5C>T · rs2543414902 · VCV2277572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.71e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8834	likely pathogenic · top 10% in ERI2
REVEL	0.134	moderately benign-leaning
SaProt	LLR -2.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 8,703 bp · p 0.00034 · regional, not allelic
Overall
CADD	27.1	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 8.71e-05% European (non-Finnish) · 1/1,148,072 alleles

Overall 7.14e-05% 1/1,400,642 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: ERI2
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_001142725
dbSNP: rs2543414902
Type: single nucleotide variant
Location: chr16:20806426 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.66 · 2 PDB

Full ERI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM3 p.Asn444His Uncertain significance ★ ⚠ same type
ACSM3 p.Gly260Ala Uncertain significance ★ ⚠ same type
ACSM3 p.Pro268Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Trp273Arg Uncertain significance ★ ⚠ same type
ACSM3 p.Tyr457Cys Uncertain significance ★ ⚠ same type
ERI2 p.Ala102Ser Uncertain significance ★ ⚠ same type
ERI2 p.Ala19Val Uncertain significance ★ ⚠ same type
ERI2 p.Ala200Val 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/eri2-p-ala2val (accessed [today's date]).

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