Is MCCC1 p.Thr596= (c.1788T>C) pathogenic?

MCCC1 p.Thr596= (c.1788T>C) is classified Likely benign in MCCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). Absent from gnomAD v4.1; Associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency.

What condition is associated with MCCC1 p.Thr596= (c.1788T>C)?

MCCC1 p.Thr596= (c.1788T>C) is associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency (ClinVar).

How common is MCCC1 p.Thr596= (c.1788T>C) in the general population?

MCCC1 p.Thr596= (c.1788T>C) is absent from gnomAD v4.1 (gnomAD).

How is 3-methylcrotonyl-CoA carboxylase deficiency inherited?

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

MCCC1 p.Thr596=

c.1788T>C · rs2530043333 · VCV3018908

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

3-methylcrotonyl-CoA carboxylase 1 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 -0.2	GERP -3.9, phastCons 0.008
Overall
CADD	2.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MCCC1
Protein: p.Thr596=
Coding: c.1788T>C
MANE Select: NM_020166
dbSNP: rs2530043333
Type: single nucleotide variant
Location: chr3:183022498 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB
Residue 596: a β-strand

Full MCCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3-methylcrotonyl-CoA carboxylase 1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 3-methylcrotonyl-CoA carboxylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MCCC1 p.Thr596Asn Uncertain significance ★ ⚠ same residue
MCCC1 c.1268-1G>A Pathogenic ★★ same condition
MCCC1 c.1268-2A>G Pathogenic ★★ same condition
MCCC1 c.137-2A>G Pathogenic/Likely pathogenic ★★ same condition
MCCC1 c.1378-2A>G Pathogenic/Likely pathogenic ★★ same condition
MCCC1 c.1594+1G>A Likely pathogenic ★★ same condition
MCCC1 c.1595-1G>C Likely pathogenic ★★ same condition
MCCC1 c.1681+2T>C Pathogenic/Likely pathogenic ★★ 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/mccc1-p-thr596 (accessed [today's date]).

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