ACAN p.Phe429=
c.1287C>T · rs559634421 · VCV732226
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.279%, eas)
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 1.6 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 6.726 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.279%
East Asian · 125/44,870 alleles
Filtering AF
0.239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.224%
Overall
0.00849%
137/1,613,546 alleles · rare
exomes 130/1,461,162 · genomes 7/152,384 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.279% | 359 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| Admixed American | 0.00167% | 59,988 |
| South Asian | 0.0011% | 91,006 |
| European (non-Finnish) | 0.000593% | 168,527 |
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.Phe429=
- Coding
- c.1287C>T
- MANE Select
- NM_001369268
- dbSNP
- rs559634421
- Type
- single nucleotide variant
- Location
- chr15:88845740 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
Similar variants
- 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
- ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Asp2419Asn Likely 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-phe429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown