ABCA4 p.Thr1526=
c.4578G>A · rs138831474 · VCV298235
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.038%, nfe)
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 -13 | GERP -4 |
| Overall | ||
| CADD | 0.874 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.038%
European (non-Finnish) · 448/1,180,018 alleles
Filtering AF
0.035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0338%
Overall
0.0309%
498/1,614,140 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.038% | 2,634 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| East Asian | 0.0267% | 3,740 |
| South Asian | 0.00769% | 13,011 |
| Admixed American | 0.00666% | 15,004 |
| African / African-American | 0.00666% | 15,006 |
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.Thr1526=
- Coding
- c.4578G>A
- MANE Select
- NM_000350
- dbSNP
- rs138831474
- Type
- single nucleotide variant
- Location
- chr1:94025010 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1526
- 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 (in stgd1; likely pathogenic; also found in a patient with chorioretinal atrophy; reduced retinal-stimulated atp hydrolysis); a β-strand
Similar variants
- ABCA4 p.Thr1526Met 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-thr1526 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown