Is ABCA4 p.Ser839= (c.2517C>T) pathogenic?

ABCA4 p.Ser839= (c.2517C>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-16). Ultra-rare (popmax 0.0178%, nfe); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Ser839= (c.2517C>T)?

ABCA4 p.Ser839= (c.2517C>T) is associated with ABCA4-related disorder (ClinVar).

How common is ABCA4 p.Ser839= (c.2517C>T) in the general population?

ABCA4 p.Ser839= (c.2517C>T) is ultra-rare (popmax 0.0178%, nfe) (gnomAD).

ABCA4 p.Ser839=

c.2517C>T · rs138246242 · VCV298256

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, nfe)

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 0.48	GERP -2.4, phastCons 0.96
Overall
CADD	6.278	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% European (non-Finnish) · 210/1,180,030 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0132% 213/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0178%	5,619
African / African-American	0.00267%	37,451
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.Ser839=
Coding: c.2517C>T
MANE Select: NM_000350
dbSNP: rs138246242
Type: single nucleotide variant
Location: chr1:94055181 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 839: 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

ABCA4-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 c.1099+2T>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.160+5G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1937+1G>C Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.1938-619A>G Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2160+1G>C Pathogenic ★★ same condition
ABCA4 c.2161-8G>A Pathogenic ★★ same condition
ABCA4 c.2382+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCA4 c.2383-1G>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-ser839 (accessed [today's date]).

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