Is ABCA2 p.Pro1593= (c.4779A>C) pathogenic?

ABCA2 p.Pro1593= (c.4779A>C) is classified Likely benign in ABCA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-24). Very rare (popmax 0.00827%, afr); Associated with ABCA2-related disorder.

What condition is associated with ABCA2 p.Pro1593= (c.4779A>C)?

ABCA2 p.Pro1593= (c.4779A>C) is associated with ABCA2-related disorder (ClinVar).

How common is ABCA2 p.Pro1593= (c.4779A>C) in the general population?

ABCA2 p.Pro1593= (c.4779A>C) is very rare (popmax 0.00827%, afr) (gnomAD).

ABCA2 p.Pro1593=

c.4779A>C · rs1383480862 · VCV3041390

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00827%, afr)

Conditions

ABCA2-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 -11	GERP -2.9
Overall
CADD	0.877	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00827% African / African-American · 5/60,494 alleles

Filtering AF 0.00321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00221%

Overall 0.00393% 41/1,043,834 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0149%	6,730
Finnishnot grpmax-eligible	0.00858%	11,658
African / African-Americangrpmax	0.00827%	12,099
Admixed American	0.00411%	24,330
European (non-Finnish)	0.00368%	27,194
South Asian	0.00129%	77,720

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCA2
Protein: p.Pro1593=
Coding: c.4779A>C
MANE Select: NM_001606
dbSNP: rs1383480862
Type: single nucleotide variant
Location: chr9:137013090 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1593: the 'disordered' region; a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCA2-related disorder

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2392Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Glu1515Lys Uncertain significance ★★ ⚠ same condition
ABCA2 p.Ser1427Arg Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2298Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Arg926Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Thr398Lys Conflicting classifications of pathogenicity ★ ⚠ 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/abca2-p-pro1593 (accessed [today's date]).

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