Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 15 submitters
gnomAD v4.1
Common
common (popmax 24.2%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
6
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 -7.5 | GERP -3.1 |
| Overall | ||
| CADD | 2.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
24.2%
African / African-American · 18,115/74,902 alleles
Filtering AF
23.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 23.8%
Overall
18%
290,706/1,611,868 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 24.2% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 20.5% | 5 |
| European (non-Finnish) | 18.3% | 5 |
| Remaining individualsnot grpmax-eligible | 17.7% | 6 |
| Finnishnot grpmax-eligible | 17.6% | 6 |
| Middle Eastern | 17.1% | 6 |
| Admixed American | 16.1% | 6 |
| Amishnot grpmax-eligible | 13.7% | 7 |
| East Asian | 13.5% | 7 |
| South Asian | 13.2% | 8 |
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.Pro1948=
- Coding
- c.5844A>G
- MANE Select
- NM_000350
- dbSNP
- rs2275029
- Type
- single nucleotide variant
- Location
- chr1:94008289 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.96 · 8 PDB
- Residue 1948
- 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); the abc transporter 2 domain; 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); a turn
Similar variants
- 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
- ABCA4 c.5018+2T>C 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-pro1948 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown