Is ABCC2 p.Ser190Ter (c.569C>A) pathogenic?

ABCC2 p.Ser190Ter (c.569C>A) is classified Pathogenic in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-26). Very rare (popmax 0.00223%, eas).

How common is ABCC2 p.Ser190Ter (c.569C>A) in the general population?

ABCC2 p.Ser190Ter (c.569C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

ABCC2 p.Ser190Ter

c.569C>A · rs1207538473 · VCV2815791

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 32
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.23	loss · gain 0.09 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.3	GERP 0.71, phastCons 0.001
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 0.00223% East Asian · 1/44,804 alleles

Overall 6.24e-05% 1/1,602,006 alleles · very rare exomes 1/1,449,820 · genomes 0/152,186 · joint denominator

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.Ser190Ter
Coding: c.569C>A
MANE Select: NM_000392
dbSNP: rs1207538473
Type: single nucleotide variant
Location: chr10:99793992 (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-p-ser190ter (accessed [today's date]).

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