Is MCCC1 p.Val64fs (c.191_192del) pathogenic?

MCCC1 p.Val64fs (c.191192del) is classified Likely pathogenic in MCCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-29). Very rare (popmax 0.00223%, eas); Associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency.

What condition is associated with MCCC1 p.Val64fs (c.191_192del)?

MCCC1 p.Val64fs (c.191_192del) is associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency (ClinVar).

How common is MCCC1 p.Val64fs (c.191_192del) in the general population?

MCCC1 p.Val64fs (c.191_192del) is very rare (popmax 0.00223%, eas) (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.Val64fs

c.191_192del · rs781572557 · VCV2676456

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

3-methylcrotonyl-CoA carboxylase 1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 6.19e-05% 1/1,614,224 alleles · very rare exomes 1/1,461,886 · genomes 0/152,338 · joint denominator

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.Val64fs
Coding: c.191_192del
MANE Select: NM_020166
dbSNP: rs781572557
Type: Deletion
Location: chr3:183092490 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB
Residue 64: the biotin carboxylation domain; an α-helix

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.Val64= Likely benign ★ same residue
MCCC1 c.1731+1del Pathogenic/Likely pathogenic ★★ same condition
MCCC1 c.1973_1977+28del Pathogenic/Likely pathogenic ★★ same condition
MCCC1 c.640_641delGG Pathogenic ★★ same condition
MCCC1 c.89+2_89+4del Likely pathogenic ★★ same condition
MCCC1 p.Ala291fs Pathogenic/Likely pathogenic ★★ same condition
MCCC1 p.Arg208fs Pathogenic/Likely pathogenic ★★ same condition
MCCC1 p.Arg544fs 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-val64fs (accessed [today's date]).

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