ABCA4 p.Trp1408Ter
c.4223G>A · rs61750134 · VCV860842
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ABCA4-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 28 of 50 |
| Splicing | ||
| SpliceAI | Δ0.27 | donor loss, 30 bp away · masked 0 · deltas |
| Pangolin | Δ0.40 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.7, phastCons 1 |
| Overall | ||
| CADD | 49.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ABCA4
- Protein
- p.Trp1408Ter
- Coding
- c.4223G>A
- MANE Select
- NM_000350
- dbSNP
- rs61750134
- Type
- single nucleotide variant
- Location
- chr1:94031026 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1408
- 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; likely pathogenic; does not affect secondary structure; decreased all-trans-retinal binding); a UniProt-annotated variant site (in stgd1; likely pathogenic; reduced retinal-stimulated atp hydrolysis); an α-helix
Similar variants
- ABCA4 p.Trp1408Leu Pathogenic ★ ⚠ same residue
- ABCA4 c.1099+2T>G Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 c.160+5G>C Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 c.1937+1G>C Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 c.1938-619A>G Pathogenic/Likely pathogenic ★★ same condition
- ABCA4 c.2160+1G>C Pathogenic ★★ same condition
- ABCA4 c.2161-8G>A Pathogenic ★★ same condition
- ABCA4 c.2382+1G>A 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-trp1408ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown