Is ABCC2 p.Ile781Met (c.2343C>G) pathogenic?

ABCC2 p.Ile781Met (c.2343C>G) is classified Uncertain significance in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-06). AlphaMissense: likely benign (0.1487); Very rare (popmax 0.005%, amr).

How common is ABCC2 p.Ile781Met (c.2343C>G) in the general population?

ABCC2 p.Ile781Met (c.2343C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Ile781Met (c.2343C>G)?

AlphaMissense predicts likely benign (score 0.1487) — an in-silico prediction, not a clinical call.

ABCC2 p.Ile781Met

c.2343C>G · rs1564688620 · VCV594820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1487	likely benign
REVEL	0.696	pathogenic-leaning
SaProt	LLR -9.10	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	23.5	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 0.005% Admixed American · 3/60,020 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000274% 4/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
Remaining individualsnot grpmax-eligible	0.0016%	62,512

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.Ile781Met
Coding: c.2343C>G
MANE Select: NM_000392
dbSNP: rs1564688620
Type: single nucleotide variant
Location: chr10:99818861 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 781: a β-strand; the abc transporter 1 domain

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

Similar variants

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
ABCC2 c.3415-1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC2 c.3741+1G>A Pathogenic/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-ile781met (accessed [today's date]).

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