CLIC5 p.Leu152=
c.456G>T · rs199809331 · VCV1318088
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0407%, nfe)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 9.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0407%
European (non-Finnish) · 476/1,170,770 alleles
Filtering AF
0.0376%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0364%
Overall
0.0307%
491/1,601,610 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0407% | 2,460 |
| Remaining individualsnot grpmax-eligible | 0.0145% | 6,873 |
| Admixed American | 0.00503% | 19,874 |
| African / African-American | 0.00401% | 24,929 |
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
- CLIC5
- Protein
- p.Leu152=
- Coding
- c.456G>T
- MANE Select
- NM_016929
- dbSNP
- rs199809331
- Type
- single nucleotide variant
- Location
- chr6:45914360 (GRCh38)
- Gene constraint
- LOEUF 1.233 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 3 PDB
Similar variants
- CLIC5 p.Arg203His Uncertain significance ★★ ⚠ same type
- CLIC5 p.Arg216Gln Uncertain significance ★★ ⚠ same type
- CLIC5 p.Arg224His Uncertain significance ★★ ⚠ same type
- CLIC5 p.Asn204Thr Uncertain significance ★★ ⚠ same type
- CLIC5 p.His54Arg Uncertain significance ★★ ⚠ same type
- CLIC5 p.Ile118Val Uncertain significance ★★ ⚠ same type
- CLIC5 p.Ile41Phe Uncertain significance ★★ ⚠ same type
- CLIC5 p.Leu96Phe 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/clic5-p-leu152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown