ACAN p.Cys643=
c.1929C>T · rs551265948 · VCV2054597
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.649%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.8 |
| Overall | ||
| CADD | 1.733 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.649%
South Asian · 590/90,968 alleles
Filtering AF
0.605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.588%
Overall
0.0387%
624/1,612,708 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.649% | 154 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,313 |
| East Asian | 0.00223% | 44,828 |
| European (non-Finnish) | 0.000509% | 196,600 |
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
- ACAN
- Protein
- p.Cys643=
- Coding
- c.1929C>T
- MANE Select
- NM_001369268
- dbSNP
- rs551265948
- Type
- single nucleotide variant
- Location
- chr15:88849634 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 643
- a disulfide bond; the 'g2-b'' region; the link 4 domain
Similar variants
- ACAN p.Cys643Ter Pathogenic ★ same residue
- ACAN p.Cys643Arg Uncertain significance ★ ⚠ same residue
- ACAN c.1733-2A>G Likely pathogenic ★★ same type
- ACAN c.630-13G>A Pathogenic ★★ same type
- ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg236Ter Pathogenic ★★ same type
- ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg394Ter Pathogenic ★★ 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/acan-p-cys643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown