Is MCCC2 p.Asn480Asp (c.1438A>G) pathogenic?

MCCC2 p.Asn480Asp (c.1438A>G) is classified Uncertain significance in MCCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1744); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with MCCC2 p.Asn480Asp (c.1438A>G)?

MCCC2 p.Asn480Asp (c.1438A>G) is associated with Inborn genetic diseases, 3-methylcrotonyl-CoA carboxylase 2 deficiency, 3-methylcrotonyl-CoA carboxylase deficiency (ClinVar).

How common is MCCC2 p.Asn480Asp (c.1438A>G) in the general population?

MCCC2 p.Asn480Asp (c.1438A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MCCC2 p.Asn480Asp (c.1438A>G)?

AlphaMissense predicts likely benign (score 0.1744) — an in-silico prediction, not a clinical call.

MCCC2 p.Asn480Asp

c.1438A>G · rs201060452 · VCV991036

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1744	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -11.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 69 kb · p 0.42 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,016 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,214 alleles · very 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.Asn480Asp
Coding: c.1438A>G
MANE Select: NM_022132
dbSNP: rs201060452
Type: single nucleotide variant
Location: chr5:71650133 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 14 PDB
Residue 480: an α-helix; 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

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

Also linked: 3-methylcrotonyl-CoA carboxylase 2 deficiency 3-methylcrotonyl-CoA carboxylase deficiency

Similar variants

MCCC2 p.Asn480Lys Uncertain significance ★ ⚠ same residue
MCCC2 p.Asn480Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MCCC2 p.Asn480= Uncertain significance same residue
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.1216+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-asn480asp (accessed [today's date]).

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