ABCA4 p.Met448fs
c.1344del · rs61748554 · VCV99047
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 10 of 50 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -0.62, phastCons 0.63 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Met448fs
- Coding
- c.1344del
- MANE Select
- NM_000350
- dbSNP
- rs61748554
- Type
- Deletion
- Location
- chr1:94078602 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 448
- 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; no effect on solubility; no effect on localization to cytoplasmic vesicle; decreased basal and n-ret-pe-stimulated atpase activity; decreased n-all-trans-retinylidenephosphatidylethanolamine binding); an α-helix; a disulfide bond
Disease context
severe early-childhood-onset retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Stargardt disease
For Severe early-childhood-onset retinal dystrophy (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy
Similar variants
- ABCA4 p.Met448Val Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ABCA4 p.Met448Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
- ABCA4 p.Asp279fs Pathogenic ★★★ same condition
- ABCA4 p.Gly1972_Val1973insTer Pathogenic ★★★ same condition
- ABCA4 p.Gly963fs Pathogenic ★★★ same condition
- ABCA4 p.Leu296fs Pathogenic ★★★ same condition
- ABCA4 c.6729+5_6729+19del Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 p.Asn1818fs 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-met448fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown