Is ABCA4 p.Arg18= (c.52C>A) pathogenic?

ABCA4 p.Arg18= (c.52C>A) is classified Likely benign in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Ultra-rare (popmax 0.018%, eas).

How common is ABCA4 p.Arg18= (c.52C>A) in the general population?

ABCA4 p.Arg18= (c.52C>A) is ultra-rare (popmax 0.018%, eas) (gnomAD).

ABCA4 p.Arg18=

c.52C>A · rs121909205 · VCV1672762

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, eas)

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 -0.023	GERP -3.6, phastCons 0.16
Overall
CADD	6.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% East Asian · 8/44,462 alleles

Filtering AF 0.00891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00646%

Overall 0.000871% 14/1,606,580 alleles · ultra-rare exomes 14/1,457,948 · genomes 0/148,632 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.018%	5,558
South Asian	0.0022%	45,460
Admixed American	0.00169%	59,084
Remaining individualsnot grpmax-eligible	0.00161%	62,176
European (non-Finnish)	0.00017%	588,474

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.Arg18=
Coding: c.52C>A
MANE Select: NM_000350
dbSNP: rs121909205
Type: single nucleotide variant
Location: chr1:94120994 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 18: an α-helix; a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (in stgd1)

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

Similar variants

ABCA4 p.Arg18Gln Pathogenic ★★ ⚠ same residue
ABCA4 p.Arg18Pro Pathogenic ★★ same residue
ABCA4 p.Arg18Trp Pathogenic ★★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
ABCA4 c.3523-1G>A Pathogenic ★★★ same type
ABCA4 c.4253+43G>A Pathogenic ★★★ same type
ABCA4 c.4254-1G>C Pathogenic ★★★ same type

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-arg18 (accessed [today's date]).

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