Is ABCA4 p.Pro564= (c.1692A>G) pathogenic?

ABCA4 p.Pro564= (c.1692A>G) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-30). Ultra-rare (popmax 0.0591%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Pro564= (c.1692A>G)?

ABCA4 p.Pro564= (c.1692A>G) is associated with Inborn genetic diseases, severe early-childhood-onset retinal dystrophy, inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Pro564= (c.1692A>G) in the general population?

ABCA4 p.Pro564= (c.1692A>G) is ultra-rare (popmax 0.0591%, nfe) (gnomAD).

ABCA4 p.Pro564=

c.1692A>G · rs143263315 · VCV236084

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0591%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.9
Overall
CADD	2.241	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0591% European (non-Finnish) · 697/1,179,970 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.054%

Overall 0.0456% 736/1,613,852 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0591%	1,693
Admixed American	0.0317%	3,157
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.0107%	9,363
Finnishnot grpmax-eligible	0.00469%	21,333

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.Pro564=
Coding: c.1692A>G
MANE Select: NM_000350
dbSNP: rs143263315
Type: single nucleotide variant
Location: chr1:94063180 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 564: 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)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe early-childhood-onset retinal dystrophy inherited retinal dystrophy

Similar variants

ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>A Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C 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-pro564 (accessed [today's date]).

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