Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 9.2%, afr) — 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. | ||
| REVEL | 0.176 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -7.8 | GERP -3 |
| Overall | ||
| CADD | 0.103 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.2%
African / African-American · 6,898/74,990 alleles
Filtering AF
9.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.94%
Overall
0.489%
7,900/1,614,098 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.2% | 11 |
| Remaining individualsnot grpmax-eligible | 0.709% | 141 |
| Admixed American | 0.653% | 153 |
| Middle Eastern | 0.379% | 264 |
| South Asian | 0.034% | 2,938 |
| European (non-Finnish) | 0.00958% | 10,443 |
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.Pro318=
- Coding
- c.954C>G
- MANE Select
- NM_001831
- dbSNP
- rs9331937
- Type
- single nucleotide variant
- Location
- chr8:27599990 (GRCh38)
- Gene constraint
- LOEUF 0.716 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.11 · 2 PDB
- Residue 318
- 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.His252= Likely 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-pro318 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown