ABCA4 p.Pro143=
c.429G>A · rs138494741 · VCV1645849
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0347%, afr)
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 -5.5 | GERP -3.2 |
| Overall | ||
| CADD | 1.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0347%
African / African-American · 26/74,892 alleles
Filtering AF
0.0243%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0208%
Overall
0.00297%
48/1,613,470 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0347% | 2,880 |
| South Asian | 0.00659% | 15,178 |
| Admixed American | 0.005% | 20,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,812 |
| East Asian | 0.00223% | 44,884 |
| European (non-Finnish) | 0.000763% | 131,109 |
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
- ABCA4
- Protein
- p.Pro143=
- Coding
- c.429G>A
- MANE Select
- NM_000350
- dbSNP
- rs138494741
- Type
- single nucleotide variant
- Location
- chr1:94108590 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 143
- a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a disulfide bond
Similar variants
- ABCA4 p.Pro143Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ABCA4 p.Pro143Ala Likely pathogenic ★ ⚠ same residue
- ABCA4 p.Pro143fs Pathogenic/Likely pathogenic ★★ same residue
- ABCA4 c.1937+1G>A Pathogenic ★★★ same type
- ABCA4 c.3328+2T>A Pathogenic ★★★ same type
- ABCA4 c.3523-1G>A Pathogenic ★★★ same type
- ABCA4 c.4253+43G>A Pathogenic ★★★ same type
- ABCA4 c.4254-1G>C 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/abca4-p-pro143 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown