Is ABCA4 p.Pro868fs (c.2603del) pathogenic?

ABCA4 p.Pro868fs (c.2603del) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00133%, afr); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Pro868fs (c.2603del)?

ABCA4 p.Pro868fs (c.2603del) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Pro868fs (c.2603del) in the general population?

ABCA4 p.Pro868fs (c.2603del) is very rare (popmax 0.00133%, afr) (gnomAD).

ABCA4 p.Pro868fs

c.2603del · rs751791095 · VCV942176

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 17 of 50
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.48	GERP -4.2, phastCons 0.14
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Overall 6.2e-05% 1/1,613,804 alleles · very rare exomes 0/1,461,588 · genomes 1/152,216 · joint denominator

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.Pro868fs
Coding: c.2603del
MANE Select: NM_000350
dbSNP: rs751791095
Type: Deletion
Location: chr1:94051683 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 868: 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); an α-helix

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

Disease context

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
ABCA4 p.Ala1324fs Pathogenic ★★ same condition
ABCA4 p.Ala222fs Pathogenic ★★ same condition
ABCA4 p.Arg1556fs Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Arg1705_Val1706insTer Pathogenic/Likely pathogenic ★★ same condition
ABCA4 p.Arg1843_Gly1844del 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-pro868fs (accessed [today's date]).

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