CLSTN3 p.Ala85=
c.255G>A · rs141936578 · VCV2642664
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0205%, 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 -6.7 | GERP -3.7 |
| Overall | ||
| CADD | 1.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0205%
European (non-Finnish) · 242/1,180,010 alleles
Filtering AF
0.0183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0175%
Overall
0.0165%
267/1,613,986 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0205% | 4,876 |
| African / African-American | 0.02% | 4,994 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,811 |
| Admixed American | 0.00333% | 29,997 |
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
- CLSTN3
- Protein
- p.Ala85=
- Coding
- c.255G>A
- MANE Select
- NM_014718
- dbSNP
- rs141936578
- Type
- single nucleotide variant
- Location
- chr12:7133640 (GRCh38)
- Gene constraint
- LOEUF 0.508 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 77.80
- Residue 85
- the cadherin 1 domain
Similar variants
- CLSTN3 p.Ala85Val Uncertain significance ★ ⚠ same residue
- CLSTN3 p.Arg806Trp Uncertain significance ★★ ⚠ same type
- CLSTN3 p.Ala11Val Uncertain significance ★ ⚠ same type
- CLSTN3 p.Ala152Val Uncertain significance ★ ⚠ same type
- CLSTN3 p.Ala153Thr Uncertain significance ★ ⚠ same type
- CLSTN3 p.Ala304Val Uncertain significance ★ ⚠ same type
- CLSTN3 p.Ala312Pro Uncertain significance ★ ⚠ same type
- CLSTN3 p.Ala312Val Uncertain significance ★ ⚠ 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/clstn3-p-ala85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown