Is ABCA4 p.Phe2245fs (c.6735del) pathogenic?

ABCA4 p.Phe2245fs (c.6735del) is classified Pathogenic in ABCA4 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-02-17). No gnomAD frequency available for this variant; Associated with inherited retinal dystrophy.

What condition is associated with ABCA4 p.Phe2245fs (c.6735del)?

ABCA4 p.Phe2245fs (c.6735del) is associated with inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Phe2245fs (c.6735del) in the general population?

ABCA4 p.Phe2245fs (c.6735del) is no gnomAD frequency available for this variant (gnomAD).

ABCA4 p.Phe2245fs

c.6735del · rs2523609688 · VCV2098035

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 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 49 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, 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.Phe2245fs
Coding: c.6735del
MANE Select: NM_000350
dbSNP: rs2523609688
Type: Deletion
Location: chr1:93996190 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 2245: 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 'essential for atp binding and atpase activity' region; 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 stgd1; uncertain significance; also found in a patient with chorioretinal atrophy; uncertain significance); an α-helix

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

Similar variants

ABCA4 p.Asp279fs Pathogenic ★★★ same condition
ABCA4 p.Gly1972_Val1973insTer Pathogenic ★★★ same condition
ABCA4 p.Leu296fs Pathogenic ★★★ same condition
ABCA4 p.Lys1033fs Pathogenic ★★★ same condition
ABCA4 p.Ser1642fs Pathogenic ★★★ same condition
ABCA4 c.6729+5_6729+19del Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Asp342fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Gln1513fs 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-phe2245fs (accessed [today's date]).

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