ACP4 p.Pro125=
c.375C>T · rs74407135 · VCV777505
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.77%, 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 -4.7 |
| Overall | ||
| CADD | 0.009 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.77%
African / African-American · 3,578/75,034 alleles
Filtering AF
4.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.58%
Overall
0.249%
4,021/1,613,146 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.77% | 21 |
| Admixed American | 0.327% | 306 |
| Remaining individualsnot grpmax-eligible | 0.301% | 332 |
| Middle Eastern | 0.115% | 866 |
| South Asian | 0.0209% | 4,793 |
| European (non-Finnish) | 0.00271% | 36,872 |
| East Asian | 0.00223% | 44,874 |
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
- ACP4
- Protein
- p.Pro125=
- Coding
- c.375C>T
- MANE Select
- NM_033068
- dbSNP
- rs74407135
- Type
- single nucleotide variant
- Location
- chr19:50791727 (GRCh38)
- Gene constraint
- LOEUF 1.413 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.30
Similar variants
- ACP4 p.Arg111Cys Pathogenic/Likely pathogenic ★★ same type
- ACP4 c.550-4C>T Benign ★★ same type
- ACP4 c.550-9C>T Benign ★★ same type
- ACP4 p.Gly328Ala Benign ★★ same type
- ACP4 c.645+1G>A Likely pathogenic ★ same type
- ACP4 p.Leu85Pro Pathogenic ★ same type
- ACP4 p.Met282Thr Pathogenic ★ ⚠ same type
- ACP4 p.Pro249Leu 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/acp4-p-pro125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown