ABCA4 p.Pro1380=
c.4140G>A · rs139109485 · VCV236108
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, sas)
Conditions
2
inherited retinal dystrophy
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 -9.8 | GERP -5.3 |
| Overall | ||
| CADD | 0.075 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
South Asian · 13/91,042 alleles
Filtering AF
0.00845%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.00266%
43/1,614,092 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0143% | 7,003 |
| Admixed American | 0.01% | 10,002 |
| European (non-Finnish) | 0.00195% | 51,304 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
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.Pro1380=
- Coding
- c.4140G>A
- MANE Select
- NM_000350
- dbSNP
- rs139109485
- Type
- single nucleotide variant
- Location
- chr1:94031109 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1380
- 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; pathogenic; also found in a patient with chorioretinal atrophy; decreased solubility; loss of cytoplasmic vesicle localization; decreased basal and n-ret-pe-stimulated atpase activity; decreased n-all-trans-retinylidenephosphatidylethanolamine binding); an α-helix; a disulfide bond
Similar variants
- ABCA4 p.Pro1380Leu Pathogenic ★★★ same residue
- ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
- ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
- ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
- ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
- ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
- ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
- ABCA4 c.5018+2T>A Pathogenic ★★★ same condition
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-pro1380 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown