ABCC4 p.Tyr499=
c.1497C>T · VCV4683817
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 25.4%, afr) — 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 -1.3 | GERP -3.4 |
| Overall | ||
| CADD | 7.367 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.4%
African / African-American · 19,011/74,878 alleles
Filtering AF
25.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25%
Overall
1.44%
23,191/1,613,700 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 25.4% | 4 |
| Middle Eastern | 2.47% | 40 |
| Remaining individualsnot grpmax-eligible | 2.01% | 50 |
| Admixed American | 1.93% | 52 |
| Ashkenazi Jewishnot grpmax-eligible | 0.841% | 119 |
| South Asian | 0.126% | 792 |
| European (non-Finnish) | 0.106% | 943 |
| Finnishnot grpmax-eligible | 0.00156% | 63,966 |
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.Tyr499=
- Coding
- c.1497C>T
- MANE Select
- NM_005845
- Type
- single nucleotide variant
- Location
- chr13:95186749 (GRCh38)
- Gene constraint
- LOEUF 0.647 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42 · 25 PDB
- Residue 499
- an α-helix; the abc transporter 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-tyr499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown