Is MCCC2 p.Ile531Phe (c.1590_1591delinsTT) pathogenic?

MCCC2 p.Ile531Phe (c.15901591delinsTT) is classified Uncertain significance in MCCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). Absent from gnomAD; Associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency.

What condition is associated with MCCC2 p.Ile531Phe (c.1590_1591delinsTT)?

MCCC2 p.Ile531Phe (c.1590_1591delinsTT) is associated with 3-methylcrotonyl-CoA carboxylase 2 deficiency (ClinVar).

How common is MCCC2 p.Ile531Phe (c.1590_1591delinsTT) in the general population?

MCCC2 p.Ile531Phe (c.1590_1591delinsTT) 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 p.Ile531Phe

c.1590_1591delinsTT · rs2112478243 · VCV1521582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	GERP -3.1, phastCons 0.8
Regional constraint	o/e 0.97	unconstrained · MANE · 69 kb · p 0.42 · regional, not allelic

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
Protein: p.Ile531Phe
Coding: c.1590_1591delinsTT
MANE Select: NM_022132
dbSNP: rs2112478243
Type: Indel
Location: chr5:71656758 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 14 PDB
Residue 531: the coa carboxyltransferase c-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.Asn395_Leu398delinsSerIleTer Pathogenic/Likely pathogenic ★★ same condition
MCCC2 p.Thr139fs Likely pathogenic ★★ same condition
MCCC2 c.511+2_511+3delinsGG Likely pathogenic ★ same condition
MCCC2 p.Glu253fs Likely pathogenic ★ same condition
MCCC2 p.His282fs Likely pathogenic ★ same condition
MCCC2 p.Pro186_Asp187delinsLeuValGluValSerVal Conflicting classifications of pathogenicity ★ same condition
MCCC2 c.1000-2A>G Likely pathogenic ★★ same condition
MCCC2 c.1072+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/mccc2-p-ile531phe (accessed [today's date]).

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