MCPH1 p.Ile481=
c.1443C>T · rs185736569 · VCV502249
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.102%, amr)
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 0.22 | GERP -0.3 |
| Overall | ||
| CADD | 2.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.102%
Admixed American · 61/60,030 alleles
Filtering AF
0.0811%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0738%
Overall
0.0039%
63/1,614,256 alleles · rare
exomes 37/1,461,884 · genomes 26/152,372 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.102% | 984 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
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.Ile481=
- Coding
- c.1443C>T
- MANE Select
- NM_024596
- dbSNP
- rs185736569
- Type
- single nucleotide variant
- Location
- chr8:6445165 (GRCh38)
- Gene constraint
- LOEUF 1.342 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 59.80 · 9 PDB
Similar variants
- MCPH1 p.Ile481Leu Uncertain significance ★ ⚠ same residue
- MCPH1 p.Ile481Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
- MCPH1 p.Ile481Thr Uncertain significance ★ ⚠ same residue
- MCPH1 p.Ile481Val 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
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-ile481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown