Is ABCC2 p.Pro1158fs (c.3472_3473del) pathogenic?

ABCC2 p.Pro1158fs (c.34723473del) is classified Pathogenic in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). Very rare (popmax 0.00401%, afr).

How common is ABCC2 p.Pro1158fs (c.3472_3473del) in the general population?

ABCC2 p.Pro1158fs (c.3472_3473del) is very rare (popmax 0.00401%, afr) (gnomAD).

ABCC2 p.Pro1158fs

c.3472_3473del · rs762291612 · VCV593494

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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 25 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,892 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,012 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.Pro1158fs
Coding: c.3472_3473del
MANE Select: NM_000392
dbSNP: rs762291612
Type: Deletion
Location: chr10:99836146 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1158: an α-helix; the abc transmembrane type-1 2 domain

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

Similar variants

ABCC2 p.Asn159fs Pathogenic ★★ same type
ABCC2 p.Asn718fs Pathogenic/Likely pathogenic ★★ same type
ABCC2 p.Ile754fs Pathogenic ★★ same type
ABCC2 p.Leu431fs Pathogenic ★★ same type
ABCC2 p.Leu788fs Pathogenic/Likely pathogenic ★★ same type
ABCC2 p.Leu809fs Pathogenic/Likely pathogenic ★★ same type
ABCC2 p.Pro194_Ser195insTer Pathogenic ★★ same type
ABCC2 p.Pro274fs 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-pro1158fs (accessed [today's date]).

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