ABCC4 p.Ile223=
c.669T>C · VCV4683822
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 87.1%, amr) — too common for a highly-penetrant pathogenic allele
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 -14 | GERP -3.5 |
| Overall | ||
| CADD | 0.344 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
87.1%
Admixed American · 52,284/60,004 alleles
Filtering AF
86.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 86.4%
Overall
85%
1,371,091/1,613,874 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 87.1% | 1 |
| European (non-Finnish) | 86.6% | 1 |
| Amishnot grpmax-eligible | 86.4% | 1 |
| Finnishnot grpmax-eligible | 85.2% | 1 |
| Remaining individualsnot grpmax-eligible | 83.3% | 1 |
| East Asian | 79.2% | 1 |
| African / African-American | 79% | 1 |
| South Asian | 74.8% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 74.5% | 1 |
| Middle Eastern | 71.9% | 1 |
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.Ile223=
- Coding
- c.669T>C
- MANE Select
- NM_005845
- Type
- single nucleotide variant
- Location
- chr13:95209550 (GRCh38)
- Gene constraint
- LOEUF 0.647 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42 · 25 PDB
- Residue 223
- an α-helix; the abc transmembrane type-1 1 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-ile223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown