CLIC5 p.Pro208=
c.624G>A · rs539916161 · VCV682565
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.032%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -4.4 |
| Overall | ||
| CADD | 2.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.032%
Admixed American · 19/59,320 alleles
Filtering AF
0.0209%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0174%
Overall
0.00286%
46/1,609,096 alleles · ultra-rare
exomes 40/1,457,054 · genomes 6/152,042 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.032% | 3,122 |
| South Asian | 0.0133% | 7,518 |
| East Asian | 0.0067% | 14,921 |
| African / African-American | 0.00401% | 24,929 |
| Finnishnot grpmax-eligible | 0.00157% | 63,856 |
| European (non-Finnish) | 0.000679% | 147,221 |
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.Pro208=
- Coding
- c.624G>A
- MANE Select
- NM_016929
- dbSNP
- rs539916161
- Type
- single nucleotide variant
- Location
- chr6:45903220 (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-pro208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown