Is MCCC2 p.Glu113del (c.335AGG[1]) pathogenic?

MCCC2 p.Glu113del (c.335AGG[1]) is classified Uncertain significance in MCCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). Ultra-rare (popmax 0.015%, amr); Associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency.

What condition is associated with MCCC2 p.Glu113del (c.335AGG[1])?

MCCC2 p.Glu113del (c.335AGG[1]) is associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency (ClinVar).

How common is MCCC2 p.Glu113del (c.335AGG[1]) in the general population?

MCCC2 p.Glu113del (c.335AGG[1]) is ultra-rare (popmax 0.015%, amr) (gnomAD).

How is 3-methylcrotonyl-CoA carboxylase deficiency inherited?

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

MCCC2 p.Glu113del

c.335AGG[1] · rs750854953 · VCV2164184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Conditions

3-methylcrotonyl-CoA carboxylase 2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -4.4
Overall
CADD	18.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,974 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000558% 9/1,614,004 alleles · ultra-rare

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: MCCC2
Protein: p.Glu113del
Coding: c.335AGG[1]
MANE Select: NM_022132
dbSNP: rs750854953
Type: Microsatellite
Location: chr5:71599711 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 14 PDB
Residue 113: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region

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 p.Val150fs Pathogenic ★★ same condition
MCCC2 p.Glu515_Glu516insGlyProGlyAlaGlyAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyTrpIleThrArgSerGlyAspXaaXaaXaaXaaLysLysLysLysLysLysLysLysPheGluGlu Pathogenic ★ same condition
MCCC2 c.1217-6_1217-3del Likely benign ★ same condition
MCCC2 c.1000-2A>G Likely pathogenic ★★ same condition
MCCC2 c.1072+1G>A Likely pathogenic ★★ same condition
MCCC2 c.1149+1G>A Pathogenic/Likely pathogenic ★★ same condition
MCCC2 c.1149+1G>T Pathogenic/Likely pathogenic ★★ same condition
MCCC2 c.1151del 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-p-glu113del (accessed [today's date]).

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