Is ABCA4 p.Ser1789Arg (c.5367C>G) pathogenic?

ABCA4 p.Ser1789Arg (c.5367C>G) is classified Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-27). AlphaMissense: likely pathogenic (0.9518); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with ABCA4 p.Ser1789Arg (c.5367C>G)?

ABCA4 p.Ser1789Arg (c.5367C>G) is associated with retinitis pigmentosa (ClinVar).

How common is ABCA4 p.Ser1789Arg (c.5367C>G) in the general population?

ABCA4 p.Ser1789Arg (c.5367C>G) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCA4 p.Ser1789Arg (c.5367C>G)?

AlphaMissense predicts likely pathogenic (score 0.9518) — an in-silico prediction, not a clinical call.

ABCA4 p.Ser1789Arg

c.5367C>G · rs2523668750 · VCV2151885

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9518 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9518	likely pathogenic ✓ concordant with ClinVar · top 5% in ABCA4
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -11.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 0.77, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA4
Protein: p.Ser1789Arg
Coding: c.5367C>G
MANE Select: NM_000350
dbSNP: rs2523668750
Type: single nucleotide variant
Location: chr1:94014636 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1789: 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); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); an α-helix

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ABCA4 p.Ser1789Asn Pathogenic ★ same residue
ABCA4 p.Ser1789Gly Likely pathogenic ★ ⚠ same residue
ABCA4 c.5460+1G>A Pathogenic ★★★ same condition
ABCA4 c.5461-10T>C Pathogenic ★★★ same condition
ABCA4 p.Ala967Val Likely pathogenic ★★★ ⚠ same condition
ABCA4 p.Arg2139Trp Pathogenic ★★★ same condition
ABCA4 p.Arg408Ter Pathogenic ★★★ same condition
ABCA4 p.Arg572Pro 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-ser1789arg (accessed [today's date]).

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