CLU p.His263=
c.789T>C · rs7982 · VCV3060904
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 76.6%, eas) — too common for a highly-penetrant pathogenic allele
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 -4.8 | GERP -5.1 |
| Overall | ||
| CADD | 0.389 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
76.6%
East Asian · 34,356/44,840 alleles
Filtering AF
75.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 75.7%
Overall
61.1%
985,550/1,613,754 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 76.6% | 1 |
| South Asian | 69.6% | 1 |
| Admixed American | 66.5% | 2 |
| Amishnot grpmax-eligible | 63.1% | 2 |
| Remaining individualsnot grpmax-eligible | 61.8% | 2 |
| Middle Eastern | 61.6% | 2 |
| European (non-Finnish) | 59.9% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 59.7% | 2 |
| Finnishnot grpmax-eligible | 59.4% | 2 |
| African / African-American | 57% | 2 |
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
- CLU
- Protein
- p.His263=
- Coding
- c.789T>C
- MANE Select
- NM_001831
- dbSNP
- rs7982
- Type
- single nucleotide variant
- Location
- chr8:27604964 (GRCh38)
- Gene constraint
- LOEUF 0.716 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.11 · 2 PDB
- Residue 263
- a disulfide bond
Similar variants
- CLU p.Ala438= Likely benign ★★ same type
- CLU p.Asn64= Likely benign ★★ same type
- CLU p.Asp328= Benign ★★ same type
- CLU p.Asp328Asn Benign ★★ same type
- CLU p.Asp397= Benign/Likely benign ★★ same type
- CLU p.His252= Likely benign ★★ same type
- CLU p.Pro318= Benign ★★ same type
- CLU p.Ser396Leu 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/clu-p-his263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown