ABCC4 p.Pro1258=
c.3774G>A · VCV4683804
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.47%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.3 |
| Overall | ||
| CADD | 4.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.47%
African / African-American · 2,603/75,042 alleles
Filtering AF
3.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.31%
Overall
0.194%
3,129/1,614,154 alleles · low-frequency
exomes 1,619/1,461,872 · genomes 1,510/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.47% | 29 |
| Middle Eastern | 0.396% | 253 |
| Admixed American | 0.247% | 406 |
| Remaining individualsnot grpmax-eligible | 0.243% | 411 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0169% | 5,922 |
| European (non-Finnish) | 0.0159% | 6,277 |
| East Asian | 0.00891% | 11,223 |
| South Asian | 0.00549% | 18,216 |
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
- ABCC4
- Protein
- p.Pro1258=
- Coding
- c.3774G>A
- MANE Select
- NM_005845
- Type
- single nucleotide variant
- Location
- chr13:95034701 (GRCh38)
- Gene constraint
- LOEUF 0.647 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42 · 25 PDB
- Residue 1258
- an α-helix; the abc transporter 2 domain
Similar variants
- ABCC4 p.Ala1282Thr Uncertain significance ★★ ⚠ same type
- ABCC4 p.Ala1324Thr Uncertain significance ★★ ⚠ same type
- ABCC4 p.Leu238Phe Uncertain significance ★★ ⚠ same type
- ABCC4 p.Tyr788Cys Uncertain significance ★★ ⚠ same type
- ABCC4 c.1825-7A>G Benign ★★ same type
- ABCC4 c.185+7C>T Benign ★★ same type
- ABCC4 c.307-10C>T Benign/Likely benign ★★ same type
- ABCC4 p.Ala700= Benign ★★ 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/abcc4-p-pro1258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown