Is ABCA4 p.Asn343= (c.1029T>C) pathogenic?

ABCA4 p.Asn343= (c.1029T>C) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-17). Rare (popmax 0.199%, nfe); Associated with severe early-childhood-onset retinal dystrophy.

What condition is associated with ABCA4 p.Asn343= (c.1029T>C)?

ABCA4 p.Asn343= (c.1029T>C) is associated with severe early-childhood-onset retinal dystrophy (ClinVar).

How common is ABCA4 p.Asn343= (c.1029T>C) in the general population?

ABCA4 p.Asn343= (c.1029T>C) is rare (popmax 0.199%, nfe) (gnomAD).

How is Severe early-childhood-onset retinal dystrophy inherited?

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

ABCA4 p.Asn343=

c.1029T>C · rs145483148 · VCV166617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.199%, nfe)

Conditions

severe early-childhood-onset retinal dystrophy

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 0.57	phastCons 0.93
Overall
CADD	2.535	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.199% European (non-Finnish) · 2,346/1,180,018 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.189%

Overall 0.162% 2,617/1,614,068 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.199%	503
Remaining individualsnot grpmax-eligible	0.162%	619
Middle Eastern	0.148%	674
South Asian	0.09%	1,111
Admixed American	0.0533%	1,875
African / African-American	0.04%	2,500
Finnishnot grpmax-eligible	0.0265%	3,767

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.Asn343=
Coding: c.1029T>C
MANE Select: NM_000350
dbSNP: rs145483148
Type: single nucleotide variant
Location: chr1:94080548 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 343: 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

severe early-childhood-onset retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe early-childhood-onset retinal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C Pathogenic ★★★ same condition
ABCA4 c.5196+1137G>A 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-asn343 (accessed [today's date]).

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