Is OXCT1 p.Ser33= (c.99C>G) pathogenic?

OXCT1 p.Ser33= (c.99C>G) is classified Likely benign in OXCT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). Rare (popmax 0.1%, amr); Associated with succinyl-CoA:3-ketoacid CoA transferase deficiency.

What condition is associated with OXCT1 p.Ser33= (c.99C>G)?

OXCT1 p.Ser33= (c.99C>G) is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency (ClinVar).

How common is OXCT1 p.Ser33= (c.99C>G) in the general population?

OXCT1 p.Ser33= (c.99C>G) is rare (popmax 0.1%, amr) (gnomAD).

OXCT1 p.Ser33=

Q: How is Succinyl-CoA:3-oxoacid CoA transferase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.99C>G · rs182901792 · VCV746743

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.1%, amr)

Conditions

succinyl-CoA:3-ketoacid CoA transferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -2.1	GERP -3.2
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% Admixed American · 60/59,880 alleles

Filtering AF 0.0799% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.0104% 168/1,608,806 alleles · rare exomes 153/1,457,314 · genomes 15/151,492 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.1%	998
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.00963%	10,389
European (non-Finnish)	0.00842%	11,879
African / African-American	0.00268%	37,313

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: OXCT1
Protein: p.Ser33=
Coding: c.99C>G
MANE Select: NM_000436
dbSNP: rs182901792
Type: single nucleotide variant
Location: chr5:41862730 (GRCh38)
Gene constraint: LOEUF 0.521 · pLI 0.97 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.33 · 1 PDB

Full OXCT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

succinyl-CoA:3-ketoacid CoA transferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Succinyl-CoA:3-oxoacid CoA transferase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

OXCT1 c.1099+2T>C Likely pathogenic ★★ same condition
OXCT1 c.278+1G>A Likely pathogenic ★★ same condition
OXCT1 p.Arg124Ter Likely pathogenic ★★ same condition
OXCT1 p.Arg468Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
OXCT1 c.671+3A>G Uncertain significance ★★ same condition
OXCT1 p.Ala401Val Uncertain significance ★★ ⚠ same condition
OXCT1 p.Ala519Thr Uncertain significance ★★ ⚠ same condition
OXCT1 p.Arg110His Uncertain significance ★★ ⚠ same condition

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/oxct1-p-ser33 (accessed [today's date]).

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