Is ABCC2 p.Gly835Glu (c.2504G>A) pathogenic?

ABCC2 p.Gly835Glu (c.2504G>A) is classified Uncertain significance in ABCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0926); Very rare (popmax 0.0078%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Gly835Glu (c.2504G>A)?

ABCC2 p.Gly835Glu (c.2504G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Gly835Glu (c.2504G>A) in the general population?

ABCC2 p.Gly835Glu (c.2504G>A) is very rare (popmax 0.0078%, nfe) (gnomAD).

What do computational predictors say about ABCC2 p.Gly835Glu (c.2504G>A)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

ABCC2 p.Gly835Glu

c.2504G>A · rs369677401 · VCV502277

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -3.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -5.5, phastCons 0.43
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	8.269	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0078% European (non-Finnish) · 92/1,180,016 alleles

Filtering AF 0.00648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.0062% 100/1,613,956 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,826
Remaining individualsnot grpmax-eligible	0.0048%	20,830
South Asian	0.00439%	22,770
Admixed American	0.00167%	59,994

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.Gly835Glu
Coding: c.2504G>A
MANE Select: NM_000392
dbSNP: rs369677401
Type: single nucleotide variant
Location: chr10:99819153 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 835: a β-strand; the abc transporter 1 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

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
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-gly835glu (accessed [today's date]).

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