CHM p.Ala549=
c.1647T>C · rs1027171328 · VCV1144377
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0463%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.82 | GERP -4, phastCons 0.99 |
| Overall | ||
| CADD | 1.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0463%
Middle Eastern · 2/4,323 alleles
Filtering AF
0.00818%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00342%
Overall
0.000166%
2/1,201,664 alleles · ultra-rare
exomes 2/1,087,901 · genomes 0/113,763 · joint denominator
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.Ala549=
- Coding
- c.1647T>C
- MANE Select
- NM_000390
- dbSNP
- rs1027171328
- Type
- single nucleotide variant
- Location
- chrX:85873175 (GRCh38)
- Structure
- AlphaFold pLDDT 81.05
Similar variants
- CHM p.Ala549Pro Uncertain significance ★★ ⚠ same residue
- CHM p.Ala549_Leu550insTer Pathogenic ★ same residue
- 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
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-ala549 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown