Is MCCC1 p.Ala44Phe (c.130_131delinsTT) pathogenic?

MCCC1 p.Ala44Phe (c.130131delinsTT) is classified Uncertain significance in MCCC1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-10-24). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with MCCC1 p.Ala44Phe (c.130_131delinsTT)?

MCCC1 p.Ala44Phe (c.130_131delinsTT) is associated with Inborn genetic diseases, 3-methylcrotonyl-CoA carboxylase 1 deficiency (ClinVar).

How common is MCCC1 p.Ala44Phe (c.130_131delinsTT) in the general population?

MCCC1 p.Ala44Phe (c.130_131delinsTT) is no gnomAD frequency available for this variant (gnomAD).

MCCC1 p.Ala44Phe

c.130_131delinsTT · rs1553868919 · VCV476393

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 2.8	GERP 1.5, phastCons 0.25
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 0.0012 · 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: MCCC1
Protein: p.Ala44Phe
Coding: c.130_131delinsTT
MANE Select: NM_020166
dbSNP: rs1553868919
Type: Indel
Location: chr3:183094564 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 3-methylcrotonyl-CoA carboxylase 1 deficiency

Similar variants

MCCC1 p.Ala44Ser Uncertain significance ★★ ⚠ same residue
MCCC1 p.Ala44Val Conflicting classifications of pathogenicity ★ ⚠ same residue
MCCC1 p.Glu179Ter Pathogenic/Likely pathogenic ★★ same condition
MCCC1 p.Asp557fs Likely pathogenic ★ same condition
MCCC1 p.Cys142fs Pathogenic ★ same condition
MCCC1 p.Glu247_Lys248delinsIleAlaTer Pathogenic ★ same condition
MCCC1 p.Gly475_His476delinsAsn Uncertain significance ★ same condition
MCCC1 c.1268-1G>A 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-ala44phe (accessed [today's date]).

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