MCPH1 p.Asp711=
c.2133T>C · rs375451164 · VCV742981
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.25 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.035 | GERP -3.6, phastCons 0.22 |
| Overall | ||
| CADD | 0.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/75,060 alleles
Filtering AF
0.00622%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.000991%
16/1,613,998 alleles · ultra-rare
exomes 8/1,461,674 · genomes 8/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,340 |
| Admixed American | 0.00666% | 15,006 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Asp711=
- Coding
- c.2133T>C
- MANE Select
- NM_024596
- dbSNP
- rs375451164
- Type
- single nucleotide variant
- Location
- chr8:6480873 (GRCh38)
- Gene constraint
- LOEUF 1.342 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 9 PDB
- Residue 711
- the brct 2 domain; an α-helix
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-asp711 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown