Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.056%, sas)
Conditions
1
ABCA4-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5 | GERP -3.7 |
| Overall | ||
| CADD | 2.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.056%
South Asian · 51/91,070 alleles
Filtering AF
0.0437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0394%
Overall
0.00384%
62/1,613,956 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.056% | 1,786 |
| East Asian | 0.00891% | 11,220 |
| Admixed American | 0.00167% | 59,994 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
| European (non-Finnish) | 0.000339% | 295,002 |
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.Ile2231=
- Coding
- c.6693C>T
- MANE Select
- NM_000350
- dbSNP
- rs1801626
- Type
- single nucleotide variant
- Location
- chr1:93997897 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 2231
- 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; uncertain significance; also found in a patient with chorioretinal atrophy; uncertain significance)
Similar variants
- ABCA4 p.Ile2231Val Uncertain significance ★ ⚠ 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-ile2231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown