Is ABCA4 p.Gln1555fs (c.4663_4664del) pathogenic?

ABCA4 p.Gln1555fs (c.46634664del) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-14). Very rare (popmax 6.87e-05%); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Gln1555fs (c.4663_4664del)?

ABCA4 p.Gln1555fs (c.4663_4664del) is associated with ABCA4-related disorder, inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Gln1555fs (c.4663_4664del) in the general population?

ABCA4 p.Gln1555fs (c.4663_4664del) is very rare (popmax 6.87e-05%) (gnomAD).

ABCA4 p.Gln1555fs

c.4663_4664del · rs2523701032 · VCV2151886

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Conditions

ABCA4-related disorder

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 32 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.097	GERP -1.3, phastCons 0.93

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.87e-05%

Overall 6.87e-05% 1/1,454,704 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA4
Protein: p.Gln1555fs
Coding: c.4663_4664del
MANE Select: NM_000350
dbSNP: rs2523701032
Type: Deletion
Location: chr1:94023389 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1555: 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); a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance)

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

Disease context

Also linked: inherited retinal dystrophy

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.4634+1del Pathogenic ★★ same condition
ABCA4 c.5899-2del Pathogenic ★★ same condition
ABCA4 c.6729+5_6729+19del 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-gln1555fs (accessed [today's date]).

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