CLCN7 p.Val779=
c.2337C>T · rs1390033295 · VCV742074
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0027%, afr)
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 |
|---|---|---|
| Pangolin | Δ0.24 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -3.3 |
| Overall | ||
| CADD | 2.371 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0027%
African / African-American · 2/74,070 alleles
Filtering AF
0.000448%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000168%
Overall
0.000694%
11/1,585,438 alleles · very rare
exomes 10/1,433,232 · genomes 1/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0027% | 37,035 |
| East Asian | 0.00232% | 43,186 |
| South Asian | 0.00229% | 43,748 |
| European (non-Finnish) | 0.000515% | 194,268 |
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
- CLCN7
- Protein
- p.Val779=
- Coding
- c.2337C>T
- MANE Select
- NM_001287
- dbSNP
- rs1390033295
- Type
- single nucleotide variant
- Location
- chr16:1446712 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 9 PDB
- Residue 779
- a β-strand; the cbs 2 domain
Similar variants
- CLCN7 p.Val779fs Likely pathogenic ★ same residue
- CLCN7 c.1448-2A>G Likely pathogenic ★★ same type
- CLCN7 c.1617+119G>A Pathogenic ★★ same type
- CLCN7 c.739-18G>A Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Gln Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg286Trp Pathogenic/Likely pathogenic ★★ same type
- CLCN7 p.Arg526Gln Likely pathogenic ★★ same type
- CLCN7 p.Arg526Trp 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/clcn7-p-val779 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown