ABCA4 p.Leu737Ter
c.2210T>A · rs1570387558 · VCV811445
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 15 of 50 |
| Splicing | ||
| SpliceAI | Δ0.74 | acceptor gain · deltas |
| Pangolin | Δ0.38 | gain · loss 0.21 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 45.0 | 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.Leu737Ter
- Coding
- c.2210T>A
- MANE Select
- NM_000350
- dbSNP
- rs1570387558
- Type
- single nucleotide variant
- Location
- chr1:94056773 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 737
- 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); an α-helix; a disulfide bond
Similar variants
- ABCA4 p.Leu737Ser Likely pathogenic ★ same residue
- ABCA4 p.Leu737Phe Uncertain significance ★ ⚠ same residue
- ABCA4 p.Leu737= Likely benign ★ 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
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-leu737ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown