Is ABCC2 p.Arg655Ter (c.1963C>T) pathogenic?

ABCC2 p.Arg655Ter (c.1963C>T) is classified Pathogenic/Likely pathogenic in ABCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00333%, amr); Associated with ABCC2-related disorder.

What condition is associated with ABCC2 p.Arg655Ter (c.1963C>T)?

ABCC2 p.Arg655Ter (c.1963C>T) is associated with ABCC2-related disorder (ClinVar).

How common is ABCC2 p.Arg655Ter (c.1963C>T) in the general population?

ABCC2 p.Arg655Ter (c.1963C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

ABCC2 p.Arg655Ter

c.1963C>T · rs780765144 · VCV1917907

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

ABCC2-related disorder

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 15 of 32
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.46, phastCons 0.27
Overall
CADD	37.0	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 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00248% 40/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
European (non-Finnish)	0.00297%	33,714
African / African-American	0.00267%	37,441
South Asian	0.0011%	91,078

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.Arg655Ter
Coding: c.1963C>T
MANE Select: NM_000392
dbSNP: rs780765144
Type: single nucleotide variant
Location: chr10:99811598 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 655: a β-strand; the abc transporter 1 domain

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

Disease context

ABCC2-related disorder

Similar variants

ABCC2 p.Arg655Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC2 p.Arg655= Likely benign ★ same residue
ABCC2 c.1967+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg1066Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg1150His Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg393Trp Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Gln1382Ter Pathogenic/Likely pathogenic ★★ same condition

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-arg655ter (accessed [today's date]).

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