Is ABCC2 p.Leu552fs (c.1655dup) pathogenic?

ABCC2 p.Leu552fs (c.1655dup) is classified Pathogenic in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Very rare (popmax 0.00167%, amr).

How common is ABCC2 p.Leu552fs (c.1655dup) in the general population?

ABCC2 p.Leu552fs (c.1655dup) is very rare (popmax 0.00167%, amr) (gnomAD).

ABCC2 p.Leu552fs

c.1655dup · rs1454680088 · VCV2877293

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3	GERP -4.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Overall 6.84e-05% 1/1,461,804 alleles · very rare

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
Protein: p.Leu552fs
Coding: c.1655dup
MANE Select: NM_000392
dbSNP: rs1454680088
Type: Duplication
Location: chr10:99807506 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 552: an α-helix; the abc transmembrane type-1 1 domain

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

Similar variants

ABCC2 p.Asp1073Ter Pathogenic ★★ same type
ABCC2 p.Leu1213fs Pathogenic ★★ same type
ABCC2 p.Lys298fs Pathogenic ★★ same type
ABCC2 p.Ser1168fs Pathogenic ★★ same type
ABCC2 p.Val667fs Pathogenic/Likely pathogenic ★★ same type
ABCC2 p.Ala579fs Pathogenic ★ same type
ABCC2 p.Asp210Ter Pathogenic ★ same type
ABCC2 p.Asp304fs 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-p-leu552fs (accessed [today's date]).

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