CLIC6 p.Ala262=
c.786G>C · VCV4533611
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0319%, 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 -8.3 | GERP -1.1 |
| Overall | ||
| CADD | 4.397 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0319%
European (non-Finnish) · 205/643,620 alleles
Filtering AF
0.0282%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0269%
Overall
0.0265%
227/856,744 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0319% | 3,140 |
| Remaining individualsnot grpmax-eligible | 0.0267% | 3,750 |
| South Asian | 0.0139% | 7,200 |
| Admixed American | 0.00879% | 11,380 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00666% | 15,012 |
| African / African-American | 0.00593% | 16,873 |
| East Asian | 0.00404% | 24,734 |
| Finnishnot grpmax-eligible | 0.00373% | 26,830 |
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
- CLIC6
- Protein
- p.Ala262=
- Coding
- c.786G>C
- MANE Select
- NM_053277
- Type
- single nucleotide variant
- Location
- chr21:34670174 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.24
- Residue 262
- the 'disordered' region; the '13 x 10 aa tandem repeat of g-d-[sng]-[vim]-[deq]-a-[eag]-[gdve]-[prg]-[lavp]' region
Similar variants
- CLIC6 p.Arg436Pro Benign ★★ same type
- CLIC6 p.Arg640Lys Benign ★★ same type
- CLIC6 p.Asp616= Benign ★★ same type
- CLIC6 p.Glu401= Likely benign ★★ same type
- CLIC6 p.Ile651Val Benign ★★ same type
- CLIC6 p.Ser550= Benign ★★ same type
- CLIC6 p.Thr667= Benign ★★ same type
- CLIC6 p.Val180Leu Benign ★★ ⚠ 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/clic6-p-ala262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown