MCCC2 p.Pro244Ala
c.730C>G · VCV4848201
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5544 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5544 | ambiguous |
|---|---|---|
| REVEL | 0.955 | strongly pathogenic-leaning |
| SaProt | LLR -11.57 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 5.1, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 69 kb · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 26.6 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MCCC2
- Protein
- p.Pro244Ala
- Coding
- c.730C>G
- MANE Select
- NM_022132
- Type
- single nucleotide variant
- Location
- chr5:71626745 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.82 · 14 PDB
- Residue 244
- an α-helix; the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region
Similar variants
- MCCC2 c.1000-2A>G Likely pathogenic ★★ same type
- MCCC2 c.1072+1G>A Likely pathogenic ★★ same type
- MCCC2 c.1149+1G>A Pathogenic/Likely pathogenic ★★ same type
- MCCC2 c.1149+1G>T Pathogenic/Likely pathogenic ★★ same type
- MCCC2 c.1216+1G>A Likely pathogenic ★★ same type
- MCCC2 c.1216+2T>A Pathogenic/Likely pathogenic ★★ same type
- MCCC2 c.1216+2T>C Likely pathogenic ★★ same type
- MCCC2 c.129+1G>T Likely pathogenic ★★ same type
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-pro244ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown