Is OGG1 p.Ser44Pro (c.130T>C) pathogenic?

OGG1 p.Ser44Pro (c.130T>C) is classified Uncertain significance in OGG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely pathogenic (0.9338); Very rare (popmax 0.00305%, nfe).

How common is OGG1 p.Ser44Pro (c.130T>C) in the general population?

OGG1 p.Ser44Pro (c.130T>C) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about OGG1 p.Ser44Pro (c.130T>C)?

AlphaMissense predicts likely pathogenic (score 0.9338) — an in-silico prediction, not a clinical call.

OGG1 p.Ser44Pro

c.130T>C · rs939255450 · VCV2493179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9338	likely pathogenic · top 7% in OGG1
REVEL	0.498	indeterminate
SaProt	LLR -15.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.76, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 6,860 bp · p 0.078 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00305% European (non-Finnish) · 36/1,180,036 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00229% 37/1,613,828 alleles · very rare exomes 36/1,461,664 · genomes 1/152,164 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00305%	32,779
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: OGG1
Protein: p.Ser44Pro
Coding: c.130T>C
MANE Select: NM_002542
dbSNP: rs939255450
Type: single nucleotide variant
Location: chr3:9750416 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.49 · 48 PDB

Full OGG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OGG1 c.949-5T>C Benign ★★ same type
CAMK1 p.Ile19Asn Uncertain significance ★ ⚠ same type
OGG1 p.Ala21Ser Uncertain significance ★ ⚠ same type
OGG1 p.Ala334Val Uncertain significance ★ ⚠ same type
OGG1 p.Arg134Gly Uncertain significance ★ same type
OGG1 p.Arg134Leu Uncertain significance ★ ⚠ same type
OGG1 p.Arg213Gln Uncertain significance ★ ⚠ same type
OGG1 p.Arg304Gln 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/ogg1-p-ser44pro (accessed [today's date]).

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