Is ABCA4 c.2653+2del pathogenic?

ABCA4 c.2653+2del is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-10). Absent from gnomAD; Associated with severe early-childhood-onset retinal dystrophy.

What condition is associated with ABCA4 c.2653+2del?

ABCA4 c.2653+2del is associated with severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 c.2653+2del in the general population?

ABCA4 c.2653+2del is absent from gnomAD (gnomAD).

How is Severe early-childhood-onset retinal dystrophy inherited?

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

ABCA4 c.2653+2del

rs766646086 · VCV1678618

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

severe early-childhood-onset retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.22	GERP 0.81, phastCons 0.97
Non-coding constraint	Z 1.96	1 kb window · o/e 0.81 · regional · uncalibrated

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
Coding: c.2653+2del
MANE Select: NM_000350
dbSNP: rs766646086
Type: Deletion
Location: chr1:94051631 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB

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

Disease context

severe early-childhood-onset retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe early-childhood-onset retinal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ABCA4 p.Gly1972_Val1973insTer Pathogenic ★★★ same condition
ABCA4 p.Gly963fs Pathogenic ★★★ same condition
ABCA4 p.Leu296fs Pathogenic ★★★ same condition
ABCA4 c.6729+5_6729+19del Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Asn1818fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Asn96fs Pathogenic ★★ same condition
ABCA4 p.Asp1613fs Pathogenic ★★ same condition
ABCA4 p.Asp342fs 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-c-2653-plus-2del (accessed [today's date]).

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