ACP4 p.Leu313=
c.939C>T · VCV3481924
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -4 |
| Overall | ||
| CADD | 0.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00428%
69/1,613,930 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| East Asian | 0.0134% | 7,479 |
| South Asian | 0.0132% | 7,591 |
| African / African-American | 0.00934% | 10,701 |
| Admixed American | 0.005% | 19,999 |
| European (non-Finnish) | 0.00322% | 31,053 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
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.Leu313=
- Coding
- c.939C>T
- MANE Select
- NM_033068
- Type
- single nucleotide variant
- Location
- chr19:50794534 (GRCh38)
- Gene constraint
- LOEUF 1.413 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.30
- Residue 313
- a disulfide bond
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 p.Pro125= Benign ★★ same type
- ACP4 c.645+1G>A Likely pathogenic ★ same type
- ACP4 p.Leu85Pro Pathogenic ★ same type
- ACP4 p.Met282Thr 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-leu313 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown