Is ABCA4 p.Arg124= (c.372T>G) pathogenic?

ABCA4 p.Arg124= (c.372T>G) is classified Likely benign in ABCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00186%, nfe).

How common is ABCA4 p.Arg124= (c.372T>G) in the general population?

ABCA4 p.Arg124= (c.372T>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

ABCA4 p.Arg124=

c.372T>G · rs745550261 · VCV2987163

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

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 -0.47	GERP -3.2
Overall
CADD	4.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,026 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,637
Admixed American	0.00167%	60,026
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Arg124=
Coding: c.372T>G
MANE Select: NM_000350
dbSNP: rs745550261
Type: single nucleotide variant
Location: chr1:94108647 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 124: a UniProt-annotated variant site (in cord3; uncertain significance); an α-helix; a disulfide bond; a UniProt-annotated variant site (in stgd1; uncertain significance)

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

Similar variants

ABCA4 p.Arg124His Uncertain significance ★★ ⚠ same residue
ABCA4 p.Arg124Gly Likely pathogenic ★ ⚠ same residue
ABCA4 p.Arg124Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg124 (accessed [today's date]).

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