MCPH1 p.Pro367=
c.1101G>A · rs201084851 · VCV1596176
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.6 |
| Overall | ||
| CADD | 0.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,894 alleles
Filtering AF
0.00223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.00254%
41/1,613,970 alleles · very rare
exomes 39/1,461,852 · genomes 2/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,447 |
| European (non-Finnish) | 0.00305% | 32,778 |
| African / African-American | 0.00267% | 37,452 |
| Admixed American | 0.00167% | 59,992 |
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
- MCPH1
- Protein
- p.Pro367=
- Coding
- c.1101G>A
- MANE Select
- NM_024596
- dbSNP
- rs201084851
- Type
- single nucleotide variant
- Location
- chr8:6444823 (GRCh38)
- Gene constraint
- LOEUF 1.342 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 9 PDB
- Residue 367
- the 'disordered' region
Similar variants
- MCPH1 p.Pro367Ala Uncertain significance ★ ⚠ same residue
- MCPH1 p.Pro367Arg Uncertain significance ★ ⚠ same residue
- MCPH1 p.Pro367Leu Uncertain significance ★ ⚠ same residue
- MCPH1 c.321+2T>C Likely pathogenic ★★ same type
- MCPH1 c.322-1G>C Pathogenic/Likely pathogenic ★★ same type
- MCPH1 p.Gln199Ter Pathogenic ★★ same type
- MCPH1 p.Gln386Ter Pathogenic/Likely pathogenic ★★ same type
- MCPH1 p.Gly245Ter Pathogenic/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/mcph1-p-pro367 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown