Is OXCT2 p.Pro46Arg (c.137C>G) pathogenic?

OXCT2 p.Pro46Arg (c.137C>G) is classified Uncertain significance in OXCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: ambiguous (0.3586); Very rare (popmax 0.00117%, sas).

How common is OXCT2 p.Pro46Arg (c.137C>G) in the general population?

OXCT2 p.Pro46Arg (c.137C>G) is very rare (popmax 0.00117%, sas) (gnomAD).

What do computational predictors say about OXCT2 p.Pro46Arg (c.137C>G)?

AlphaMissense predicts ambiguous (score 0.3586) — an in-silico prediction, not a clinical call.

OXCT2 p.Pro46Arg

c.137C>G · rs777810352 · VCV2235712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3586 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00117%, sas)

Computational evidence

Protein change
AlphaMissense	0.3586	ambiguous
REVEL	0.423	indeterminate
SaProt	LLR -13.83	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.92, phastCons 0.53
Regional constraint	o/e 0.56	unconstrained · MANE · 163 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	23.1	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 0.00117% South Asian · 1/85,226 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.00045% 7/1,556,704 alleles · very rare exomes 6/1,407,554 · genomes 1/149,150 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,354
South Asiangrpmax	0.00117%	85,226
European (non-Finnish)	0.000438%	228,218

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro46Arg
Coding: c.137C>G
MANE Select: NM_022120
dbSNP: rs777810352
Type: single nucleotide variant
Location: chr1:39771119 (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.Ala504Pro 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

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-pro46arg (accessed [today's date]).

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