Is OXCT1 p.Ala2= (c.6G>A) pathogenic?

OXCT1 p.Ala2= (c.6G>A) is classified Likely benign in OXCT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-17). Ultra-rare (popmax 0.0156%, eas); Associated with succinyl-CoA:3-ketoacid CoA transferase deficiency.

What condition is associated with OXCT1 p.Ala2= (c.6G>A)?

OXCT1 p.Ala2= (c.6G>A) is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency (ClinVar).

How common is OXCT1 p.Ala2= (c.6G>A) in the general population?

OXCT1 p.Ala2= (c.6G>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

OXCT1 p.Ala2=

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.6G>A · rs773250207 · VCV3017288

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

succinyl-CoA:3-ketoacid CoA transferase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -2.8, phastCons 0.58
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,860 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000496% 8/1,613,124 alleles · ultra-rare exomes 7/1,460,932 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
European (non-Finnish)	8.48e-05%	1,179,709

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.Ala2=
Coding: c.6G>A
MANE Select: NM_000436
dbSNP: rs773250207
Type: single nucleotide variant
Location: chr5:41870353 (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-ala2 (accessed [today's date]).

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