Is ABCC2 p.Thr244Met (c.731C>T) pathogenic?

ABCC2 p.Thr244Met (c.731C>T) is classified Uncertain significance in ABCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-24). AlphaMissense: likely benign (0.0737); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Thr244Met (c.731C>T)?

ABCC2 p.Thr244Met (c.731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Thr244Met (c.731C>T) in the general population?

ABCC2 p.Thr244Met (c.731C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Thr244Met (c.731C>T)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

ABCC2 p.Thr244Met

c.731C>T · VCV3356993

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.49	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 -5.5	GERP -5.1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	2.527	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 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00217% 35/1,614,144 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,010
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,874
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	75,032

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.Thr244Met
Coding: c.731C>T
MANE Select: NM_000392
Type: single nucleotide variant
Location: chr10:99797195 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 244: 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.Thr244= 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
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-thr244met (accessed [today's date]).

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