Is ABCC2 p.Val1363Ala (c.4088T>C) pathogenic?

ABCC2 p.Val1363Ala (c.4088T>C) is classified Uncertain significance in ABCC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-26). AlphaMissense: likely benign (0.1768); Ultra-rare (popmax 0.0484%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Val1363Ala (c.4088T>C)?

ABCC2 p.Val1363Ala (c.4088T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Val1363Ala (c.4088T>C) in the general population?

ABCC2 p.Val1363Ala (c.4088T>C) is ultra-rare (popmax 0.0484%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Val1363Ala (c.4088T>C)?

AlphaMissense predicts likely benign (score 0.1768) — an in-silico prediction, not a clinical call.

ABCC2 p.Val1363Ala

c.4088T>C · rs571273081 · VCV2341015

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1768 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0484%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1768	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -11.90	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	24.7	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 0.0484% Admixed American · 29/59,880 alleles

Filtering AF 0.0346% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00273% 44/1,612,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0484%	2,065
Middle Eastern	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.008%	12,495
African / African-American	0.00403%	24,821
South Asian	0.0011%	90,966
European (non-Finnish)	0.000424%	235,919

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.Val1363Ala
Coding: c.4088T>C
MANE Select: NM_000392
dbSNP: rs571273081
Type: single nucleotide variant
Location: chr10:99845724 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 1363: the abc transporter 2 domain

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

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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
ABCC2 p.Arg768Gln Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg934Trp Uncertain significance ★★ ⚠ same condition
ABCC2 p.Asp1021Asn 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-val1363ala (accessed [today's date]).

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