ABCA4 p.Leu1769=
c.5307G>C · rs146443426 · VCV1572291
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.246%, 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 -4.1 | GERP -2.8 |
| Overall | ||
| CADD | 0.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.246%
African / African-American · 184/74,930 alleles
Filtering AF
0.217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.205%
Overall
0.0125%
202/1,613,272 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.246% | 407 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| Admixed American | 0.01% | 9,995 |
| South Asian | 0.0011% | 90,930 |
| European (non-Finnish) | 8.48e-05% | 1,179,546 |
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.Leu1769=
- Coding
- c.5307G>C
- MANE Select
- NM_000350
- dbSNP
- rs146443426
- Type
- single nucleotide variant
- Location
- chr1:94015744 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1769
- a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance); a UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); an α-helix
Similar variants
- ABCA4 p.Leu1769Met Uncertain significance ★ ⚠ 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
- ABCA4 c.4352+1G>A Pathogenic ★★★ same type
- ABCA4 c.4773+3A>G 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-leu1769 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown