Is OXCT2 p.Ala504Pro (c.1510G>C) pathogenic?

OXCT2 p.Ala504Pro (c.1510G>C) is classified Uncertain significance in OXCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.2785); Very rare (popmax 0.00839%, amr).

How common is OXCT2 p.Ala504Pro (c.1510G>C) in the general population?

OXCT2 p.Ala504Pro (c.1510G>C) is very rare (popmax 0.00839%, amr) (gnomAD).

What do computational predictors say about OXCT2 p.Ala504Pro (c.1510G>C)?

AlphaMissense predicts likely benign (score 0.2785) — an in-silico prediction, not a clinical call.

OXCT2 p.Ala504Pro

c.1510G>C · rs200253131 · VCV3207535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00839%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2785	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -12.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.5	GERP -1.6
Regional constraint	o/e 0.21	constrained · MANE · 84 bp · p 1.4e-06 · regional, not allelic
Overall
CADD	7.782	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 0.00839% Admixed American · 5/59,578 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00379% 61/1,610,140 alleles · very rare exomes 54/1,457,964 · genomes 7/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00839%	11,916
Remaining individualsnot grpmax-eligible	0.00482%	20,763
European (non-Finnish)	0.0045%	22,228

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: OXCT2
Protein: p.Ala504Pro
Coding: c.1510G>C
MANE Select: NM_022120
dbSNP: rs200253131
Type: single nucleotide variant
Location: chr1:39769746 (GRCh38)
Structure: AlphaFold pLDDT 92.20

Full OXCT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OXCT2 p.Ala237Thr Uncertain significance ★ ⚠ same type
OXCT2 p.Ala23Val Uncertain significance ★ ⚠ same type
OXCT2 p.Ala292Thr Uncertain significance ★ ⚠ same type
OXCT2 p.Ala29Asp Uncertain significance ★ ⚠ same type
OXCT2 p.Arg146His Uncertain significance ★ ⚠ same type
OXCT2 p.Arg173Ser Uncertain significance ★ same type
OXCT2 p.Arg187Gln Uncertain significance ★ same type
OXCT2 p.Arg204Leu 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/oxct2-p-ala504pro (accessed [today's date]).

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