Is ABCA1 c.5506+252C>T pathogenic?

ABCA1 c.5506+252C>T is classified Benign in ABCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-08-30). Common (popmax 77.9%, nfe) — too common for a highly-penetrant pathogenic allele.

ABCA1 c.5506+252C>T

Q: How common is ABCA1 c.5506+252C>T in the general population?

ABCA1 c.5506+252C>T is common (popmax 77.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2740482 · VCV1182140

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 77.9%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +252	deep intronic (+252 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -2.6
Overall
CADD	0.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 77.9% European (non-Finnish) · 52,824/67,788 alleles

Filtering AF 77.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 77.1%

Overall 68.2% 103,307/151,538 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	84.7%	1
Ashkenazi Jewishnot grpmax-eligible	79.1%	1
Amishnot grpmax-eligible	78.5%	1
European (non-Finnish)grpmax	77.9%	1
Admixed American	76.5%	1
Remaining individualsnot grpmax-eligible	68.9%	1
South Asian	64.2%	2
East Asian	59.6%	2
Middle Eastern	57.9%	2
African / African-American	45.3%	2

Finnish 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: ABCA1
Coding: c.5506+252C>T
MANE Select: NM_005502
dbSNP: rs2740482
Type: single nucleotide variant
Location: chr9:104794135 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCA1 c.4274+1G>A Likely pathogenic ★★ same type
ABCA1 c.5237+3A>C Likely pathogenic ★★ same type
ABCA1 p.Arg2080Trp Likely pathogenic ★★ same type
ABCA1 p.Arg557Ter Pathogenic/Likely pathogenic ★★ same type
ABCA1 p.Arg587Trp Pathogenic/Likely pathogenic ★★ same type
ABCA1 p.Asn1800His Pathogenic/Likely pathogenic ★★ ⚠ same type
ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same type

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/abca1-c-5506-plus-252c-t (accessed [today's date]).

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