CLIC6 p.Arg245=
c.735G>C · rs763696583 · VCV2652636
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0799%, mid)
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 -2.8 | GERP -0.47 |
| Overall | ||
| CADD | 4.942 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0799%
Middle Eastern · 3/3,756 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0115%
Overall
0.000645%
8/1,240,062 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0799% | 1,252 |
| Remaining individualsnot grpmax-eligible | 0.00374% | 26,763 |
| European (non-Finnish) | 0.000278% | 360,260 |
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.Arg245=
- Coding
- c.735G>C
- MANE Select
- NM_053277
- dbSNP
- rs763696583
- Type
- single nucleotide variant
- Location
- chr21:34670123 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.24
- Residue 245
- 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.Arg245Gln Uncertain significance ★ ⚠ same residue
- CLIC6 p.Arg245Trp Uncertain significance ★ ⚠ 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-arg245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown