ACAN p.Thr184=
c.552G>A · rs142615277 · VCV730334
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.57%, afr)
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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.57%
African / African-American · 1,179/74,936 alleles
Filtering AF
1.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.47%
Overall
0.0876%
1,406/1,605,494 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.57% | 64 |
| Admixed American | 0.196% | 509 |
| Remaining individualsnot grpmax-eligible | 0.106% | 941 |
| Middle Eastern | 0.0661% | 1,513 |
| South Asian | 0.0056% | 17,845 |
| European (non-Finnish) | 0.00298% | 33,605 |
| East Asian | 0.00224% | 44,604 |
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.Thr184=
- Coding
- c.552G>A
- MANE Select
- NM_001369268
- dbSNP
- rs142615277
- Type
- single nucleotide variant
- Location
- chr15:88840109 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 184
- a disulfide bond; the link 1 domain; the 'g1-b' region
Similar variants
- ACAN p.Thr184Met 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
- ACAN p.Arg675Ter 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-thr184 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown