ABCA4 p.Arg653fs
c.1957del · VCV3250276
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
inherited retinal dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 50 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 0.98, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ABCA4
- Protein
- p.Arg653fs
- Coding
- c.1957del
- MANE Select
- NM_000350
- Type
- Deletion
- Location
- chr1:94060740 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 653
- 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 (in stgd1; likely pathogenic; severely decreased, if any, n-ret-pe-stimulated atpase activity although basal activity is unchanged; decreased n-retinylidene-phosphatidylethanolamine flippase activity; severely decreased n-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle); a UniProt-annotated variant site (in stgd1; likely pathogenic; severely decreased n-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and n-ret-pe-stimulated atpase activity); a binding site; an α-helix; a disulfide bond
Similar variants
- ABCA4 p.Arg653Cys Pathogenic ★★★ ⚠ same residue
- ABCA4 p.Arg653Leu Likely pathogenic ★★ ⚠ same residue
- ABCA4 p.Asp279fs Pathogenic ★★★ same condition
- ABCA4 p.Gly1972_Val1973insTer Pathogenic ★★★ same condition
- ABCA4 p.Leu296fs Pathogenic ★★★ same condition
- ABCA4 p.Lys1033fs Pathogenic ★★★ same condition
- ABCA4 p.Ser1642fs Pathogenic ★★★ same condition
- ABCA4 c.6729+5_6729+19del Pathogenic/Likely 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-arg653fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown