ABCA4 p.Ile1802=
c.5406C>T · rs202199507 · VCV298228
ClinGen expert panel — ABCA4 VCEP
Uncertain Significance for ABCA4-related retinopathy. Applied ACMG criteria (verbatim):
PM2_Supporting
Curation rationale (ClinGen, verbatim)
The NM_000350.3(ABCA4):c.5406C>T is a synonymous variant (p.Ile1802=). The total minor allele frequency in gnomAD v4.1.0 is 0.000039652 (64/1614042 alleles), which is lower than the ClinGen ABCA4 VCEP’s threshold for PM2_Supporting (<0.0001). The SpliceAI predictor score for this variant is 0.13, which is greater than 0.1, the ABCA4 VCEP's threshold for BP7 or BP4 criterion. To our knowledge, this variant has not been reported in the literature in any individuals with ABCA4-related retinopathy. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0.0): PM2_Supporting.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -1.4 |
| Overall | ||
| CADD | 7.903 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,413 |
| European (non-Finnish) | 0.00415% | 24,082 |
| Admixed American | 0.00333% | 30,008 |
| Finnishnot grpmax-eligible | 0.00312% | 32,016 |
| African / African-American | 0.00267% | 37,454 |
| South Asian | 0.0022% | 45,542 |
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.Ile1802=
- Coding
- c.5406C>T
- MANE Select
- NM_000350
- dbSNP
- rs202199507
- Type
- single nucleotide variant
- Location
- chr1:94014597 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1802
- 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); an α-helix
Similar variants
- ABCA4 p.Ile1802Val Uncertain significance ★★ ⚠ same residue
- ABCA4 p.Ile1802Thr Uncertain significance ★ ⚠ same residue
- ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
- ABCA4 c.3328+2T>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
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-ile1802 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown