Is MCCC1 p.Asp424= (c.1272C>T) pathogenic?

MCCC1 p.Asp424= (c.1272C>T) is classified Likely benign in MCCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Ultra-rare (popmax 0.0165%, mid); Associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency.

What condition is associated with MCCC1 p.Asp424= (c.1272C>T)?

MCCC1 p.Asp424= (c.1272C>T) is associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency (ClinVar).

How common is MCCC1 p.Asp424= (c.1272C>T) in the general population?

MCCC1 p.Asp424= (c.1272C>T) is ultra-rare (popmax 0.0165%, mid) (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.Asp424=

c.1272C>T · rs779316162 · VCV1085164

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 1	GERP -2.9, phastCons 0.99
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00109% 16/1,461,848 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,880
African / African-American	0.00133%	75,058
South Asian	0.0011%	91,082
European (non-Finnish)	0.000763%	131,113

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: MCCC1
Protein: p.Asp424=
Coding: c.1272C>T
MANE Select: NM_020166
dbSNP: rs779316162
Type: single nucleotide variant
Location: chr3:183039131 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB
Residue 424: the biotin carboxylation domain

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.Asp424Asn 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-asp424 (accessed [today's date]).

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