ABCA4 p.Ala1794Asp
c.5381C>A · rs61751406 · VCV99371
Computational evidence
| Protein change | ||
| AlphaMissense | 0.907 | likely pathogenic ✓ concordant with ClinVar · top 9% in ABCA4 |
|---|---|---|
| REVEL | 0.801 | moderately pathogenic-leaning |
| SaProt | LLR -13.78 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 0.76, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic |
| Overall | ||
| CADD | 29.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| European (non-Finnish)grpmax | 0.00271% | 36,876 |
| Admixed American | 0.00167% | 60,014 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Ala1794Asp
- Coding
- c.5381C>A
- MANE Select
- NM_000350
- dbSNP
- rs61751406
- Type
- single nucleotide variant
- Location
- chr1:94014622 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1794
- 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 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); a UniProt-annotated variant site (in stgd1; also found in a patient with bull's eye maculopathy; likely pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; decreased basal and n-ret-pe-stimulated atpase activity; decreased n-all-trans-retinylidenephosphatidylethanolamine binding); a UniProt-annotated variant site (in stgd1; likely pathogenic; loss of cytoplasmic vesicle localization; decreases basal and n-ret-pe-stimulated atpase activity; decreases solubility; reduces n-all-trans-retinylidenephosphatidylethanolamine binding); an α-helix
Similar variants
- ABCA4 p.Ala1794Pro 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-ala1794asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown