Is MCCC2 c.281+1del pathogenic?

MCCC2 c.281+1del is classified Likely pathogenic in MCCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-02). Absent from gnomAD; Associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency.

What condition is associated with MCCC2 c.281+1del?

MCCC2 c.281+1del is associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency (ClinVar).

How common is MCCC2 c.281+1del in the general population?

MCCC2 c.281+1del is absent from gnomAD (gnomAD).

How is 3-methylcrotonyl-CoA carboxylase deficiency inherited?

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

MCCC2 c.281+1del

rs2530712355 · VCV2676486

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

3-methylcrotonyl-CoA carboxylase 2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.77	GERP 2.5, phastCons 0.95
Non-coding constraint	Z -0.77	1 kb window · o/e 1.06 · regional · uncalibrated

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MCCC2
Coding: c.281+1del
MANE Select: NM_022132
dbSNP: rs2530712355
Type: Deletion
Location: chr5:71596363 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 14 PDB

Full MCCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3-methylcrotonyl-CoA carboxylase 2 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

MCCC2 c.1151del Likely pathogenic ★★ same condition
MCCC2 c.383+2del Likely pathogenic ★★ same condition
MCCC2 c.739del Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Asn230fs Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Gly118del Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Gly368fs Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Gly79fs Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Ser471fs 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/mccc2-c-281-plus-1del (accessed [today's date]).

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