Is ABCC2 p.Arg255Trp (c.763C>T) pathogenic?

ABCC2 p.Arg255Trp (c.763C>T) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-03). AlphaMissense: likely benign (0.1101); Ultra-rare (popmax 0.0183%, amr).

How common is ABCC2 p.Arg255Trp (c.763C>T) in the general population?

ABCC2 p.Arg255Trp (c.763C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Arg255Trp (c.763C>T)?

AlphaMissense predicts likely benign (score 0.1101) — an in-silico prediction, not a clinical call.

ABCC2 p.Arg255Trp

c.763C>T · rs147494662 · VCV597315

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1101	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.83	donor gain · deltas
Pangolin	Δ0.58	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.67	GERP -1.6
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,020 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.0139% 225/1,614,116 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,456
European (non-Finnish)	0.0165%	6,051
South Asian	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0048%	20,836
African / African-American	0.004%	25,009

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.Arg255Trp
Coding: c.763C>T
MANE Select: NM_000392
dbSNP: rs147494662
Type: single nucleotide variant
Location: chr10:99797227 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 255: an α-helix; the 'disordered' region

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

Similar variants

ABCC2 p.Arg255Gln Uncertain significance ★ ⚠ same residue
ABCC2 p.Arg255= Likely benign ★ same residue
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

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-arg255trp (accessed [today's date]).

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