CLCN3 p.Val484=
c.1452C>T · VCV4083934
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.033 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -8.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.077 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000867%
14/1,613,914 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00167% | 59,994 |
| European (non-Finnish) | 0.00102% | 98,328 |
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
- CLCN3
- Protein
- p.Val484=
- Coding
- c.1452C>T
- MANE Select
- NM_001829
- Type
- single nucleotide variant
- Location
- chr4:169697623 (GRCh38)
- Gene constraint
- LOEUF 0.341 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.95 · 5 PDB
Similar variants
- CLCN3 p.Ile607Val Likely pathogenic ★★ same type
- CLCN3 p.Thr570Ile Likely pathogenic ★★ ⚠ same type
- CLCN3 p.Val324Ala Likely pathogenic ★★ same type
- CLCN3 c.2367-2099A>C Uncertain significance ★★ same type
- CLCN3 p.Asn788Ser Uncertain significance ★★ ⚠ same type
- CLCN3 p.Asp485Asn Uncertain significance ★★ ⚠ same type
- CLCN3 p.Lys186Glu Uncertain significance ★★ ⚠ same type
- CLCN3 p.Pro465Thr 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/clcn3-p-val484 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown