Is ABCC2 p.Arg905Lys (c.2714G>A) pathogenic?

ABCC2 p.Arg905Lys (c.2714G>A) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.0542%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Arg905Lys (c.2714G>A)?

ABCC2 p.Arg905Lys (c.2714G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Arg905Lys (c.2714G>A) in the general population?

ABCC2 p.Arg905Lys (c.2714G>A) is ultra-rare (popmax 0.0542%, nfe) (gnomAD).

What do computational predictors say about ABCC2 p.Arg905Lys (c.2714G>A)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

ABCC2 p.Arg905Lys

c.2714G>A · rs201874841 · VCV502695

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0542%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	23.1	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 0.0542% European (non-Finnish) · 639/1,180,030 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0492%

Overall 0.0422% 681/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0542%	1,847
Finnishnot grpmax-eligible	0.0312%	3,202
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.0117%	8,575
African / African-American	0.004%	25,017
South Asian	0.0011%	91,082

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.Arg905Lys
Coding: c.2714G>A
MANE Select: NM_000392
dbSNP: rs201874841
Type: single nucleotide variant
Location: chr10:99830400 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 905: an α-helix

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.Arg905Ile Uncertain significance ⚠ 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
ABCC2 p.Arg768Gln Uncertain significance ★★ ⚠ same condition
ABCC2 p.Arg934Trp 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-arg905lys (accessed [today's date]).

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