ACAN p.Pro38=
c.114G>A · rs367956651 · VCV1601690
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0923%, 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 -15 | GERP -3.5 |
| Overall | ||
| CADD | 0.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0923%
African / African-American · 69/74,756 alleles
Filtering AF
0.0747%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0684%
Overall
0.0101%
162/1,606,596 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0923% | 1,083 |
| South Asian | 0.0155% | 6,432 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,775 |
| Admixed American | 0.01% | 9,967 |
| European (non-Finnish) | 0.00528% | 18,957 |
| Finnishnot grpmax-eligible | 0.00314% | 31,835 |
| East Asian | 0.00223% | 44,804 |
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.Pro38=
- Coding
- c.114G>A
- MANE Select
- NM_001369268
- dbSNP
- rs367956651
- Type
- single nucleotide variant
- Location
- chr15:88838706 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 38
- a β-strand; the ig-like v-type domain
Similar variants
- ACAN p.Pro38Leu Conflicting classifications of pathogenicity ★ same residue
- ACAN p.Pro38Thr 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-pro38 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown