Is ABCA4 p.Asn247= (c.741C>T) pathogenic?

ABCA4 p.Asn247= (c.741C>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-31). Rare (popmax 0.131%, sas); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Asn247= (c.741C>T)?

ABCA4 p.Asn247= (c.741C>T) is associated with ABCA4-related disorder, retinitis pigmentosa (ClinVar).

How common is ABCA4 p.Asn247= (c.741C>T) in the general population?

ABCA4 p.Asn247= (c.741C>T) is rare (popmax 0.131%, sas) (gnomAD).

ABCA4 p.Asn247=

c.741C>T · rs372976742 · VCV298266

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.131%, sas)

Conditions

ABCA4-related disorder

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 -3.1	GERP -3.8
Overall
CADD	3.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% South Asian · 119/91,080 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.015% 242/1,614,182 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.131%	765
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00949%	10,536
East Asian	0.00223%	44,870
Admixed American	0.00167%	60,034
Finnishnot grpmax-eligible	0.00156%	64,016

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.Asn247=
Coding: c.741C>T
MANE Select: NM_000350
dbSNP: rs372976742
Type: single nucleotide variant
Location: chr1:94098821 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 247: 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 (in stgd1); a β-strand; a disulfide bond

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

Disease context

Also linked: retinitis pigmentosa

Similar variants

ABCA4 p.Asn247Thr Uncertain significance ★★ ⚠ same residue
ABCA4 p.Asn247Ser Conflicting classifications of pathogenicity ★ ⚠ 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-asn247 (accessed [today's date]).

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