CHM p.Leu35Pro
c.104T>C · VCV4951928
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9991 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
CHM-related disorders
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9991 | likely pathogenic ✓ concordant with ClinVar · top 1% in CHM |
|---|---|---|
| REVEL | 0.96 | strongly pathogenic-leaning |
| SaProt | LLR -15.11 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.9, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic |
| Overall | ||
| CADD | 27.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CHM
- Protein
- p.Leu35Pro
- Coding
- c.104T>C
- MANE Select
- NM_000390
- Type
- single nucleotide variant
- Location
- chrX:86027503 (GRCh38)
- Structure
- AlphaFold pLDDT 81.05
Disease context
CHM-related disorders
Similar variants
- CHM p.Leu35= Likely benign ★ same residue
- CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same condition
- CHM c.1167-2A>G Pathogenic ★★ same condition
- CHM c.1244+2T>A Pathogenic/Likely pathogenic ★★ same condition
- CHM c.1349+1G>T Pathogenic/Likely pathogenic ★★ same condition
- CHM c.1511-1G>A Pathogenic ★★ same condition
- CHM c.1511-2A>T Likely pathogenic ★★ same condition
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-leu35pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown