Is ABCC2 c.1668+148A>G pathogenic?

ABCC2 c.1668+148A>G is classified Benign in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). Common (popmax 43.7%, afr) — too common for a highly-penetrant pathogenic allele.

ABCC2 c.1668+148A>G

Q: How common is ABCC2 c.1668+148A>G in the general population?

ABCC2 c.1668+148A>G is common (popmax 43.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2073337 · VCV1289402

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 43.7%, afr) — 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 +148	deep intronic (+148 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.6
Non-coding constraint	Z 2.66	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.7% African / African-American · 28,476/65,230 alleles

Filtering AF 43.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.1%

Overall 38.1% 435,550/1,142,614 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	50.2%	2
African / African-Americangrpmax	43.7%	2
Ashkenazi Jewishnot grpmax-eligible	40.4%	2
European (non-Finnish)	38.5%	3
South Asian	38.3%	3
Remaining individualsnot grpmax-eligible	38.2%	3
Admixed American	37.6%	3
Middle Eastern	36.5%	3
Finnishnot grpmax-eligible	36.2%	3
East Asian	22.7%	4

Amish 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: ABCC2
Coding: c.1668+148A>G
MANE Select: NM_000392
dbSNP: rs2073337
Type: single nucleotide variant
Location: chr10:99807669 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB

Full ABCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC2 c.1031+4A>G Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.1967+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.1968-1G>C Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.333+1G>A Likely pathogenic ★★ same type
ABCC2 c.3414+1G>A Likely pathogenic ★★ same type
ABCC2 c.3415-1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.3741+1G>A 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/abcc2-c-1668-plus-148a-g (accessed [today's date]).

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