ACMSD p.Pro255=
c.765G>A · rs138304352 · VCV3058305
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.032%, afr)
Conditions
1
ACMSD-related disorder
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 0.83 | GERP -2.3, phastCons 0.96 |
| Overall | ||
| CADD | 10.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.032%
African / African-American · 24/75,034 alleles
Filtering AF
0.022%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.00576%
93/1,614,092 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.032% | 3,126 |
| East Asian | 0.0201% | 4,984 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| European (non-Finnish) | 0.00441% | 22,693 |
| Admixed American | 0.00167% | 59,994 |
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
- ACMSD
- Protein
- p.Pro255=
- Coding
- c.765G>A
- MANE Select
- NM_138326
- dbSNP
- rs138304352
- Type
- single nucleotide variant
- Location
- chr2:134872557 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.67 · 6 PDB
- Residue 255
- an α-helix
Disease context
ACMSD-related disorder
Similar variants
- ACMSD p.Pro255Leu Uncertain significance ★ ⚠ same residue
- ACMSD p.Trp83Cys Uncertain significance ★ ⚠ same condition
- ACMSD c.486+10G>A Likely benign same condition
- ACMSD p.Pro11= Benign ★★ same type
- ACMSD c.677-14G>T Uncertain significance ★ same type
- ACMSD c.948+1G>A Uncertain significance ★ same type
- ACMSD p.Ala101Thr Uncertain significance ★ ⚠ same type
- ACMSD p.Ala121Val Uncertain significance ★ ⚠ 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/acmsd-p-pro255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown