Is MCCC1 p.Ser8= (c.24G>T) pathogenic?

MCCC1 p.Ser8= (c.24G>T) is classified Likely benign in MCCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Very rare (popmax 0.00323%, nfe); Associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency.

What condition is associated with MCCC1 p.Ser8= (c.24G>T)?

MCCC1 p.Ser8= (c.24G>T) is associated with 3-methylcrotonyl-CoA carboxylase 1 deficiency (ClinVar).

How common is MCCC1 p.Ser8= (c.24G>T) in the general population?

MCCC1 p.Ser8= (c.24G>T) is very rare (popmax 0.00323%, nfe) (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.Ser8=

c.24G>T · rs745696684 · VCV2146163

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00323%, nfe)

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 -3.6	GERP -3.1
Overall
CADD	1.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00323% European (non-Finnish) · 38/1,178,134 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00243% 39/1,607,468 alleles · very rare exomes 39/1,455,116 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00323%	31,004
Remaining individualsnot grpmax-eligible	0.00161%	62,138

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.Ser8=
Coding: c.24G>T
MANE Select: NM_020166
dbSNP: rs745696684
Type: single nucleotide variant
Location: chr3:183099417 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB

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 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
MCCC1 c.1682-1G>A 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-ser8 (accessed [today's date]).

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