CLIC6 p.Ser219Arg
c.657C>A · VCV4654388
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3747 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3747 | ambiguous |
|---|---|---|
| REVEL | 0.012 | strongly benign-leaning |
| SaProt | LLR -10.64 | damaging |
| ⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.7 | GERP -1.7 |
| Regional constraint | o/e 0.48 | unconstrained · MANE · 206 bp · p 2.3e-08 · regional, not allelic |
| Overall | ||
| CADD | 4.644 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CLIC6
- Protein
- p.Ser219Arg
- Coding
- c.657C>A
- MANE Select
- NM_053277
- Type
- single nucleotide variant
- Location
- chr21:34670045 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.24
- Residue 219
- 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.Ser219Gly 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
- CLIC6 p.Thr667= 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-ser219arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown