Is OXCT2 p.Pro16Ser (c.46C>T) pathogenic?

OXCT2 p.Pro16Ser (c.46C>T) is classified Uncertain significance in OXCT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.0767); Very rare (popmax 0.00416%, afr).

How common is OXCT2 p.Pro16Ser (c.46C>T) in the general population?

OXCT2 p.Pro16Ser (c.46C>T) is very rare (popmax 0.00416%, afr) (gnomAD).

What do computational predictors say about OXCT2 p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

OXCT2 p.Pro16Ser

c.46C>T · VCV3303754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00416%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -5.97	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 -0.046	GERP -1.8
Regional constraint	o/e 0.56	unconstrained · MANE · 163 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	2.553	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 0.00416% African / African-American · 3/72,122 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000506%

Overall 0.000327% 5/1,529,174 alleles · very rare exomes 5/1,377,204 · genomes 0/151,970 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00416%	24,041
Remaining individualsnot grpmax-eligible	0.00339%	29,527

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.Pro16Ser
Coding: c.46C>T
MANE Select: NM_022120
Type: single nucleotide variant
Location: chr1:39771210 (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-pro16ser (accessed [today's date]).

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