Is ABCA4 p.Arg487Pro (c.1460G>C) pathogenic?

ABCA4 p.Arg487Pro (c.1460G>C) is classified Uncertain significance in ABCA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0928); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Arg487Pro (c.1460G>C)?

ABCA4 p.Arg487Pro (c.1460G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA4 p.Arg487Pro (c.1460G>C) in the general population?

ABCA4 p.Arg487Pro (c.1460G>C) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about ABCA4 p.Arg487Pro (c.1460G>C)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

ABCA4 p.Arg487Pro

c.1460G>C · rs145614671 · VCV1051526

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -3.6
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,918 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.000991% 16/1,614,034 alleles · ultra-rare exomes 8/1,461,874 · genomes 8/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,351
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Arg487Pro
Coding: c.1460G>C
MANE Select: NM_000350
dbSNP: rs145614671
Type: single nucleotide variant
Location: chr1:94077784 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 487: 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

Similar variants

ABCA4 p.Arg487Trp Uncertain significance ★★ ⚠ same residue
ABCA4 p.Arg487Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 p.Ala1287Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala1324Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1170Thr Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg140Pro Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1963His Uncertain significance ★★ ⚠ 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-arg487pro (accessed [today's date]).

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