Is ABCC2 p.Arg768Gln (c.2303G>A) pathogenic?

ABCC2 p.Arg768Gln (c.2303G>A) is classified Uncertain significance in ABCC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-22). AlphaMissense: likely pathogenic (0.8968); Ultra-rare (popmax 0.0223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Arg768Gln (c.2303G>A)?

ABCC2 p.Arg768Gln (c.2303G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Arg768Gln (c.2303G>A) in the general population?

ABCC2 p.Arg768Gln (c.2303G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about ABCC2 p.Arg768Gln (c.2303G>A)?

AlphaMissense predicts likely pathogenic (score 0.8968) — an in-silico prediction, not a clinical call.

ABCC2 p.Arg768Gln

c.2303G>A · rs536840524 · VCV593506

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8968	likely pathogenic
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.63, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,888 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00316% 51/1,613,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
South Asian	0.00659%	15,179
African / African-American	0.00534%	18,719
Admixed American	0.00333%	29,996
European (non-Finnish)	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg768Gln
Coding: c.2303G>A
MANE Select: NM_000392
dbSNP: rs536840524
Type: single nucleotide variant
Location: chr10:99818821 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 768: an α-helix; the abc transporter 1 domain; a UniProt-annotated variant site (in djs)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC2 p.Arg768Trp Pathogenic/Likely pathogenic ★★ same residue
ABCC2 p.Arg768Pro Uncertain significance ★ ⚠ same residue
ABCC2 p.Arg768= Likely benign ★ same residue
ABCC2 p.Arg1023Ile Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg152Trp Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg393Gln Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg590His Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg612Gln Uncertain significance ★★ ⚠ 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-arg768gln (accessed [today's date]).

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