Is ERP29 p.Glu239Asp (c.717G>C) pathogenic?

ERP29 p.Glu239Asp (c.717G>C) is classified Uncertain significance in ERP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1523); Very rare (popmax 0.0022%, sas).

How common is ERP29 p.Glu239Asp (c.717G>C) in the general population?

ERP29 p.Glu239Asp (c.717G>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ERP29 p.Glu239Asp (c.717G>C)?

AlphaMissense predicts likely benign (score 0.1523) — an in-silico prediction, not a clinical call.

ERP29 p.Glu239Asp

c.717G>C · VCV4250958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1523	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -4.8, phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 9,183 bp · p 0.022 · regional, not allelic
Overall
CADD	16.35	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
African / African-American	0.00133%	74,916

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.Glu239Asp
Coding: c.717G>C
MANE Select: NM_006817
Type: single nucleotide variant
Location: chr12:112022583 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.16 · 3 PDB
Residue 239: an α-helix

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.Ala2Val 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

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-glu239asp (accessed [today's date]).

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