Is ABCA4 p.Trp1461Ter (c.4383G>A) pathogenic?

ABCA4 p.Trp1461Ter (c.4383G>A) is classified Pathogenic in ABCA4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-06). Very rare (popmax 8.48e-05%, nfe); Associated with retinitis pigmentosa.

What condition is associated with ABCA4 p.Trp1461Ter (c.4383G>A)?

ABCA4 p.Trp1461Ter (c.4383G>A) is associated with retinitis pigmentosa, retinitis pigmentosa 19 (ClinVar).

How common is ABCA4 p.Trp1461Ter (c.4383G>A) in the general population?

ABCA4 p.Trp1461Ter (c.4383G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

ABCA4 p.Trp1461Ter

c.4383G>A · rs1347261858 · VCV871796

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 30 of 50
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	46.0	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 8.48e-05% European (non-Finnish) · 1/1,179,916 alleles

Overall 6.84e-05% 1/1,461,644 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.Trp1461Ter
Coding: c.4383G>A
MANE Select: NM_000350
dbSNP: rs1347261858
Type: single nucleotide variant
Location: chr1:94029601 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1461: 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; a disulfide bond

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

Also linked: retinitis pigmentosa 19

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.Trp1461Arg Pathogenic ★ same residue
ABCA4 p.Trp1461Cys Conflicting classifications of pathogenicity ★ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5196+1137G>A Pathogenic ★★★ same condition
ABCA4 c.5460+1G>A Pathogenic ★★★ same condition
ABCA4 c.5461-10T>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-trp1461ter (accessed [today's date]).

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