Is ABCA4 p.Asn99fs (c.296dup) pathogenic?

ABCA4 p.Asn99fs (c.296dup) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-11-02). Absent from gnomAD; Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Asn99fs (c.296dup)?

ABCA4 p.Asn99fs (c.296dup) is associated with inherited retinal dystrophy, severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Asn99fs (c.296dup) in the general population?

ABCA4 p.Asn99fs (c.296dup) is absent from gnomAD (gnomAD).

ABCA4 p.Asn99fs

c.296dup · rs62645948 · VCV99181

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

inherited 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 3 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP -0.47, 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.Asn99fs
Coding: c.296dup
MANE Select: NM_000350
dbSNP: rs62645948
Type: Duplication
Location: chr1:94111443 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 99: a disulfide bond; a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (in cord3; uncertain significance)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe early-childhood-onset retinal dystrophy

Similar variants

ABCA4 p.Ala1791fs Pathogenic ★★★ same condition
ABCA4 p.Ser1071fs Pathogenic ★★★ same condition
ABCA4 p.Gly1110fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Ser84fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Thr1726fs Pathogenic ★★ same condition
ABCA4 p.Val2236fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.571_580dup Pathogenic ★ same condition
ABCA4 p.Leu1902fs 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-asn99fs (accessed [today's date]).

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