ACAN p.Arg173=
c.519G>T · rs368963320 · VCV733175
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0439%, 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 3.4 | GERP -0.2, phastCons 1 |
| Overall | ||
| CADD | 8.199 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0439%
European (non-Finnish) · 516/1,174,572 alleles
Filtering AF
0.0408%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0395%
Overall
0.0344%
551/1,603,050 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0439% | 2,276 |
| Remaining individualsnot grpmax-eligible | 0.0355% | 2,819 |
| Admixed American | 0.0102% | 9,794 |
| African / African-American | 0.00668% | 14,976 |
| Finnishnot grpmax-eligible | 0.00158% | 63,106 |
| South Asian | 0.00113% | 88,880 |
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.Arg173=
- Coding
- c.519G>T
- MANE Select
- NM_001369268
- dbSNP
- rs368963320
- Type
- single nucleotide variant
- Location
- chr15:88840076 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 173
- an α-helix; the link 1 domain; the 'g1-b' region
Similar variants
- ACAN p.Arg173Trp Uncertain significance ★★ ⚠ same residue
- ACAN p.Arg173Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- ACAN p.Arg173fs Likely pathogenic ★ 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
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-arg173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown