CLCN2 p.Phe481=
c.1443C>T · rs897101997 · VCV3009160
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.127 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.38 | acceptor gain · deltas |
| Pangolin | Δ0.20 | gain · loss 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 0.6, phastCons 1 |
| Overall | ||
| CADD | 16.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
African / African-American · 1/73,312 alleles
Overall
6.31e-05%
1/1,585,756 alleles · very rare
exomes 0/1,436,312 · genomes 1/149,444 · 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
- CLCN2
- Protein
- p.Phe481=
- Coding
- c.1443C>T
- MANE Select
- NM_004366
- dbSNP
- rs897101997
- Type
- single nucleotide variant
- Location
- chr3:184354612 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.82 · 8 PDB
Similar variants
- CLCN2 c.898+1G>A Likely pathogenic ★★ same type
- CLCN2 p.Arg172Gln Pathogenic ★★ same type
- CLCN2 p.Arg610Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN2 p.Glu619Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN2 p.Gly24Asp Pathogenic/Likely pathogenic ★★ ⚠ same type
- CLCN2 p.Trp570Ter Pathogenic/Likely pathogenic ★★ same type
- CLCN2 c.1171-3T>C Uncertain significance ★★ same type
- CLCN2 c.1721+4C>T Uncertain significance ★★ 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/clcn2-p-phe481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown