Is ERP29 p.Ala2Val (c.5C>T) pathogenic?

ERP29 p.Ala2Val (c.5C>T) is classified Uncertain significance in ERP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: ambiguous (0.5261); Very rare (popmax 0.00223%, eas).

How common is ERP29 p.Ala2Val (c.5C>T) in the general population?

ERP29 p.Ala2Val (c.5C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ERP29 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.5261) — an in-silico prediction, not a clinical call.

ERP29 p.Ala2Val

c.5C>T · VCV4019662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5261	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -9.15	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 9,183 bp · p 0.022 · regional, not allelic
Overall
CADD	24.8	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 · 1/44,752 alleles

Overall 0.000137% 2/1,459,032 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,752
European (non-Finnish)	8.48e-05%	1,178,632

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: ERP29
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_006817
Type: single nucleotide variant
Location: chr12:112013470 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.16 · 3 PDB

Full ERP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERP29 p.Ser80Leu Uncertain significance ★★ ⚠ same type
ERP29 p.Ala218Thr Uncertain significance ★ ⚠ same type
ERP29 p.Ala3Thr Uncertain significance ★ ⚠ same type
ERP29 p.Ala9Ser Uncertain significance ★ ⚠ same type
ERP29 p.Arg177His Uncertain significance ★ ⚠ same type
ERP29 p.Asp61Asn Uncertain significance ★ ⚠ same type
ERP29 p.Asp84Asn Uncertain significance ★ ⚠ same type
ERP29 p.Gln183His 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/erp29-p-ala2val (accessed [today's date]).

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