CLIC6 p.Gly263=
c.789G>A · VCV4533612
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, 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 -1.8 | GERP -0.47 |
| Overall | ||
| CADD | 5.939 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
European (non-Finnish) · 69/646,108 alleles
Filtering AF
0.00858%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00786%
Overall
0.00907%
78/859,866 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0107% | 9,364 |
| Remaining individualsnot grpmax-eligible | 0.00887% | 11,278 |
| Finnishnot grpmax-eligible | 0.00745% | 13,430 |
| South Asian | 0.00552% | 18,102 |
| East Asian | 0.00403% | 24,808 |
| African / African-American | 0.00197% | 50,726 |
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.Gly263=
- Coding
- c.789G>A
- MANE Select
- NM_053277
- Type
- single nucleotide variant
- Location
- chr21:34670177 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.24
- Residue 263
- 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.Gly263Arg Uncertain significance ⚠ same residue
- CLIC6 p.Gly263_Ala272del Benign ★ same residue
- 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
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-gly263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown