Is ABCA4 p.Arg1108fs (c.3323del) pathogenic?

ABCA4 p.Arg1108fs (c.3323del) is classified Likely pathogenic in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-30). Absent from gnomAD; Associated with severe early-childhood-onset retinal dystrophy.

What condition is associated with ABCA4 p.Arg1108fs (c.3323del)?

ABCA4 p.Arg1108fs (c.3323del) is associated with severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Arg1108fs (c.3323del) in the general population?

ABCA4 p.Arg1108fs (c.3323del) 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 p.Arg1108fs

c.3323del · rs1660527879 · VCV1048162

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 22 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.31	GERP -5.3, phastCons 0.039

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.Arg1108fs
Coding: c.3323del
MANE Select: NM_000350
dbSNP: rs1660527879
Type: Deletion
Location: chr1:94042766 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1108: 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 1 domain; a UniProt-annotated variant site (in stgd1 and ffm); a UniProt-annotated variant site (in stgd1); a disulfide bond

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.Arg1108Cys Pathogenic ★★★ ⚠ same residue
ABCA4 p.Arg1108His Pathogenic ★★★ ⚠ same residue
ABCA4 p.Arg1108Leu Pathogenic/Likely pathogenic ★★ same residue
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

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-arg1108fs (accessed [today's date]).

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