CLU p.His252=
c.756C>T · rs367989790 · VCV729718
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.175%, amr)
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 0.48 | GERP 0.027, phastCons 0.4 |
| Overall | ||
| CADD | 7.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.175%
Admixed American · 105/60,010 alleles
Filtering AF
0.148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.138%
Overall
0.00966%
156/1,614,116 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.175% | 572 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,946 |
| European (non-Finnish) | 0.00314% | 31,892 |
| African / African-American | 0.00267% | 37,517 |
| East Asian | 0.00223% | 44,868 |
| South Asian | 0.0022% | 45,537 |
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.His252=
- Coding
- c.756C>T
- MANE Select
- NM_001831
- dbSNP
- rs367989790
- Type
- single nucleotide variant
- Location
- chr8:27604997 (GRCh38)
- Gene constraint
- LOEUF 0.716 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.11 · 2 PDB
- Residue 252
- a disulfide bond; an α-helix
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.Pro318= Benign ★★ same type
- CLU p.Ser396Leu Benign ★★ ⚠ same type
- CLU p.Thr203Ile Likely 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-his252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown