Is OGA p.Pro526Ala (c.1576C>G) pathogenic?

OGA p.Pro526Ala (c.1576C>G) is classified Uncertain significance in OGA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). AlphaMissense: ambiguous (0.3943); Absent from gnomAD v4.1.

How common is OGA p.Pro526Ala (c.1576C>G) in the general population?

OGA p.Pro526Ala (c.1576C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OGA p.Pro526Ala (c.1576C>G)?

AlphaMissense predicts ambiguous (score 0.3943) — an in-silico prediction, not a clinical call.

OGA p.Pro526Ala

c.1576C>G · rs2065356434 · VCV2478445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3943	ambiguous
REVEL	0.239	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,325 bp · p 0.00049 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OGA
Protein: p.Pro526Ala
Coding: c.1576C>G
MANE Select: NM_012215
dbSNP: rs2065356434
Type: single nucleotide variant
Location: chr10:101799075 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 29 PDB

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

Similar variants

OGA c.1037-3C>T Likely benign ★★ same type
OGA p.Ala25Pro Uncertain significance ★ ⚠ same type
OGA p.Ala25Val Uncertain significance ★ ⚠ same type
OGA p.Ala27Val Uncertain significance ★ ⚠ same type
OGA p.Ala33Val Uncertain significance ★ ⚠ same type
OGA p.Ala45Val Uncertain significance ★ ⚠ same type
OGA p.Ala490Val Uncertain significance ★ ⚠ same type
OGA p.Ala51Val 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/oga-p-pro526ala (accessed [today's date]).

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