Is ABCA4 p.Trp589fs (c.1765del) pathogenic?

ABCA4 p.Trp589fs (c.1765del) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-03-08). Absent from gnomAD; Associated with cone-rod dystrophy 3.

What condition is associated with ABCA4 p.Trp589fs (c.1765del)?

ABCA4 p.Trp589fs (c.1765del) is associated with cone-rod dystrophy 3 (ClinVar).

How common is ABCA4 p.Trp589fs (c.1765del) in the general population?

ABCA4 p.Trp589fs (c.1765del) is absent from gnomAD (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCA4 p.Trp589fs

c.1765del · rs1557787559 · VCV587379

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cone-rod dystrophy 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCA4
Protein: p.Trp589fs
Coding: c.1765del
MANE Select: NM_000350
dbSNP: rs1557787559
Type: Deletion
Location: chr1:94062749 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 589: 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)

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCA4 p.Gly963fs Pathogenic ★★★ same condition
ABCA4 c.6729+5_6729+19del Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Gly1032fs Pathogenic ★★ same condition
ABCA4 p.Ile1671fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Lys223fs Pathogenic ★★ same condition
ABCA4 p.Pro1660_Leu1661insTer Pathogenic ★★ same condition
ABCA4 p.Thr2061fs Pathogenic ★★ same condition
ABCA4 p.Thr685_Leu686insTer 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-trp589fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown