Is ABCA2 p.Leu2388= (c.7164C>T) pathogenic?

ABCA2 p.Leu2388= (c.7164C>T) is classified Likely benign in ABCA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-05). Very rare (popmax 0.00273%, nfe); Associated with ABCA2-related disorder.

What condition is associated with ABCA2 p.Leu2388= (c.7164C>T)?

ABCA2 p.Leu2388= (c.7164C>T) is associated with ABCA2-related disorder (ClinVar).

How common is ABCA2 p.Leu2388= (c.7164C>T) in the general population?

ABCA2 p.Leu2388= (c.7164C>T) is very rare (popmax 0.00273%, nfe) (gnomAD).

ABCA2 p.Leu2388=

c.7164C>T · rs766516205 · VCV3058730

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00273%, nfe)

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 0.41	GERP -2.9, phastCons 0.99
Overall
CADD	6.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00273% European (non-Finnish) · 32/1,173,472 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00225% 36/1,598,560 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00273%	36,671
African / African-American	0.00268%	37,367
Remaining individualsnot grpmax-eligible	0.00162%	61,880
South Asian	0.00113%	88,560

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.Leu2388=
Coding: c.7164C>T
MANE Select: NM_001606
dbSNP: rs766516205
Type: single nucleotide variant
Location: chr9:137008527 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 2388: 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-leu2388 (accessed [today's date]).

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