CLIC6 p.Glu401=
c.1203G>A · rs375245256 · VCV718259
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.147%, 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 0.45 | GERP 0.004, phastCons 0.044 |
| Overall | ||
| CADD | 3.826 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.147%
European (non-Finnish) · 1,675/1,138,666 alleles
Filtering AF
0.141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.139%
Overall
0.119%
1,821/1,528,940 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.147% | 680 |
| Admixed American | 0.118% | 847 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0888% | 1,126 |
| Remaining individualsnot grpmax-eligible | 0.0696% | 1,438 |
| Middle Eastern | 0.0402% | 2,490 |
| African / African-American | 0.0166% | 6,021 |
| Finnishnot grpmax-eligible | 0.0106% | 9,447 |
| South Asian | 0.00614% | 16,276 |
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.Glu401=
- Coding
- c.1203G>A
- MANE Select
- NM_053277
- dbSNP
- rs375245256
- Type
- single nucleotide variant
- Location
- chr21:34670591 (GRCh38)
- Gene constraint
- LOEUF 1.445 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.24
- Residue 401
- the 'disordered' region
Similar variants
- CLIC6 p.Glu401Gly Uncertain significance ★ ⚠ same residue
- CLIC6 p.Arg436Pro Benign ★★ same type
- CLIC6 p.Arg640Lys Benign ★★ same type
- CLIC6 p.Asp616= 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-glu401 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown