CHM p.Leu433=
c.1299C>T · rs185514039 · VCV772569
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.148%, amr)
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 · G>T here scores Δ0.39 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.26 | GERP -3.8, phastCons 0.002 |
| Overall | ||
| CADD | 1.555 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
Admixed American · 67/45,142 alleles
Filtering AF
0.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.109%
Overall
0.00616%
74/1,202,228 alleles · rare
exomes 36/1,090,826 · genomes 38/111,402 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.148% | 674 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,324 |
| African / African-American | 0.00176% | 56,969 |
| European (non-Finnish) | 0.000561% | 178,133 |
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
- CHM
- Protein
- p.Leu433=
- Coding
- c.1299C>T
- MANE Select
- NM_000390
- dbSNP
- rs185514039
- Type
- single nucleotide variant
- Location
- chrX:85901134 (GRCh38)
- Structure
- AlphaFold pLDDT 81.05
Similar variants
- CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same type
- CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same type
- CHM c.1166+1G>A Pathogenic ★★ same type
- CHM c.1166+1G>C Pathogenic ★★ same type
- CHM c.1167-2A>G Pathogenic ★★ same type
- CHM c.1244+1G>A Pathogenic ★★ same type
- CHM c.1244+2T>A Pathogenic/Likely pathogenic ★★ same type
- CHM c.1349+1G>T 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/chm-p-leu433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown