Is ABCA4 p.Pro1401= (c.4203C>T) pathogenic?

ABCA4 p.Pro1401= (c.4203C>T) is classified Benign/Likely benign in ABCA4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.59%, eas); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Pro1401= (c.4203C>T)?

ABCA4 p.Pro1401= (c.4203C>T) is associated with ABCA4-related disorder, inherited retinal dystrophy (ClinVar).

How common is ABCA4 p.Pro1401= (c.4203C>T) in the general population?

ABCA4 p.Pro1401= (c.4203C>T) is low-frequency (popmax 1.59%, eas) (gnomAD).

ABCA4 p.Pro1401=

c.4203C>T · rs1801666 · VCV255922

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, eas)

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 -2.5	GERP -5.3
Overall
CADD	2.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.59% East Asian · 713/44,870 alleles

Filtering AF 1.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.45%

Overall 0.0488% 787/1,614,118 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.59%	63
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.00666%	15,007
South Asian	0.00439%	22,767
European (non-Finnish)	0.00356%	28,095
Admixed American	0.00167%	60,014

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.Pro1401=
Coding: c.4203C>T
MANE Select: NM_000350
dbSNP: rs1801666
Type: single nucleotide variant
Location: chr1:94031046 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1401: 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 (found in a patient with macular dystrophy; uncertain significance); an α-helix; a disulfide bond

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

Disease context

Also linked: inherited retinal dystrophy

Similar variants

ABCA4 p.Pro1401Ala Uncertain significance ★ ⚠ same residue
ABCA4 c.1937+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>A Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C 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-pro1401 (accessed [today's date]).

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