MCPH1 p.Lys368=
c.1104G>A · rs548110255 · VCV1611695
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.029%, 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 0.15 | GERP -3.6 |
| Overall | ||
| CADD | 0.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.029%
East Asian · 13/44,882 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.000929%
15/1,614,110 alleles · ultra-rare
exomes 10/1,461,870 · genomes 5/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.029% | 3,452 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 8.47e-05% | 1,180,025 |
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.Lys368=
- Coding
- c.1104G>A
- MANE Select
- NM_024596
- dbSNP
- rs548110255
- Type
- single nucleotide variant
- Location
- chr8:6444826 (GRCh38)
- Gene constraint
- LOEUF 1.342 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 9 PDB
- Residue 368
- the 'disordered' region
Similar variants
- 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
- MCPH1 p.Leu542Ter Pathogenic/Likely pathogenic ★★ same type
- MCPH1 p.Lys105Ter Pathogenic/Likely pathogenic ★★ same type
- MCPH1 p.Ser233Ter 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-lys368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown