CLU p.Ala438=
c.1314G>T · rs144959547 · VCV713115
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.257%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -11 |
| Overall | ||
| CADD | 0.146 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.257%
African / African-American · 193/74,992 alleles
Filtering AF
0.228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.216%
Overall
0.0139%
224/1,614,038 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.257% | 389 |
| Middle Eastern | 0.0661% | 1,514 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| Admixed American | 0.015% | 6,669 |
| European (non-Finnish) | 0.000169% | 590,009 |
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.Ala438=
- Coding
- c.1314G>T
- MANE Select
- NM_001831
- dbSNP
- rs144959547
- Type
- single nucleotide variant
- Location
- chr8:27598486 (GRCh38)
- Gene constraint
- LOEUF 0.716 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.11 · 2 PDB
- Residue 438
- an α-helix
Similar variants
- 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
- 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-ala438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown