MCPH1 p.Asp314=
c.942C>T · rs746979032 · VCV3023795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
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 -2 | GERP -2.2 |
| Overall | ||
| CADD | 1.172 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,072 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00161%
26/1,613,910 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,060 |
| African / African-American | 0.00534% | 18,729 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00167% | 60,006 |
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.Asp314=
- Coding
- c.942C>T
- MANE Select
- NM_024596
- dbSNP
- rs746979032
- Type
- single nucleotide variant
- Location
- chr8:6444664 (GRCh38)
- Gene constraint
- LOEUF 1.342 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 9 PDB
- Residue 314
- a UniProt-annotated variant site (in); the 'disordered' region
Similar variants
- MCPH1 p.Asp314His Benign ★★ 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
- MCPH1 p.Leu542Ter Pathogenic/Likely pathogenic ★★ same type
- MCPH1 p.Lys105Ter 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-asp314 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown