Is ABCC2 p.Thr336Arg (c.1007C>G) pathogenic?

ABCC2 p.Thr336Arg (c.1007C>G) is classified Uncertain significance in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-28). AlphaMissense: likely benign (0.3243); Absent from gnomAD v4.1.

How common is ABCC2 p.Thr336Arg (c.1007C>G) in the general population?

ABCC2 p.Thr336Arg (c.1007C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC2 p.Thr336Arg (c.1007C>G)?

AlphaMissense predicts likely benign (score 0.3243) — an in-silico prediction, not a clinical call.

ABCC2 p.Thr336Arg

c.1007C>G · rs149854486 · VCV502766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3243 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3243	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.73	gain · loss 0.36 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.6	GERP -5.1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	17.43	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC2
Protein: p.Thr336Arg
Coding: c.1007C>G
MANE Select: NM_000392
dbSNP: rs149854486
Type: single nucleotide variant
Location: chr10:99799346 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 336: a turn; the abc transmembrane type-1 1 domain

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

Similar variants

ABCC2 p.Thr336= Conflicting classifications of pathogenicity ★ same residue
ABCC2 p.Thr336Met Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-thr336arg (accessed [today's date]).

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