CLCN4 p.Ala517=
c.1551A>C · rs757820245 · VCV415735
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0284%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -4.5 |
| Overall | ||
| CADD | 0.935 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0284%
Admixed American · 13/45,716 alleles
Filtering AF
0.0168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0133%
Overall
0.00968%
117/1,208,165 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0284% | 3,517 |
| European (non-Finnish) | 0.0113% | 8,854 |
| Remaining individualsnot grpmax-eligible | 0.00421% | 23,764 |
| African / African-American | 0.00176% | 56,907 |
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
- CLCN4
- Protein
- p.Ala517=
- Coding
- c.1551A>C
- MANE Select
- NM_001830
- dbSNP
- rs757820245
- Type
- single nucleotide variant
- Location
- chrX:10212628 (GRCh38)
- Structure
- AlphaFold pLDDT 84.66
Similar variants
- CLCN4 p.Ala517Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLCN4 c.844-1G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN4 p.Ala555Val Pathogenic ★★ same type
- CLCN4 p.Arg718Trp Pathogenic ★★ same type
- CLCN4 p.Asp89Asn Pathogenic/Likely pathogenic ★★ same type
- CLCN4 p.Gly467Ser Likely pathogenic ★★ same type
- CLCN4 p.Gly544Arg Pathogenic ★★ same type
- CLCN4 p.Gly731Arg 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/clcn4-p-ala517 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown