Is OGA p.Pro394Ser (c.1180C>T) pathogenic?

OGA p.Pro394Ser (c.1180C>T) is classified Uncertain significance in OGA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.1732); Ultra-rare (popmax 0.0143%, sas).

How common is OGA p.Pro394Ser (c.1180C>T) in the general population?

OGA p.Pro394Ser (c.1180C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about OGA p.Pro394Ser (c.1180C>T)?

AlphaMissense predicts likely benign (score 0.1732) — an in-silico prediction, not a clinical call.

OGA p.Pro394Ser

c.1180C>T · VCV4125283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1732	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -3.23	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 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,325 bp · p 0.00049 · regional, not allelic
Overall
CADD	24.5	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 0.0143% South Asian · 13/91,048 alleles

Filtering AF 0.00845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000868% 14/1,613,772 alleles · ultra-rare exomes 13/1,461,612 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,004
European (non-Finnish)	8.48e-05%	1,179,852

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: OGA
Protein: p.Pro394Ser
Coding: c.1180C>T
MANE Select: NM_012215
Type: single nucleotide variant
Location: chr10:101800257 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 29 PDB
Residue 394: an α-helix

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-pro394ser (accessed [today's date]).

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