ABCC4 p.Asp1256=
c.3768T>C · VCV4683805
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.08%, amr)
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 4.2 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 8.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.08%
Admixed American · 48/60,002 alleles
Filtering AF
0.0619%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0575%
Overall
0.0514%
829/1,614,122 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.08% | 1,250 |
| European (non-Finnish) | 0.0627% | 1,595 |
| Remaining individualsnot grpmax-eligible | 0.0448% | 2,232 |
| African / African-American | 0.0147% | 6,813 |
| Finnishnot grpmax-eligible | 0.00312% | 32,020 |
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.Asp1256=
- Coding
- c.3768T>C
- MANE Select
- NM_005845
- Type
- single nucleotide variant
- Location
- chr13:95034707 (GRCh38)
- Gene constraint
- LOEUF 0.647 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42 · 25 PDB
- Residue 1256
- a β-strand; 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-asp1256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown