Is ABCC2 p.Lys68Thr (c.203A>C) pathogenic?

ABCC2 p.Lys68Thr (c.203A>C) is classified Conflicting classifications of pathogenicity in ABCC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-09). AlphaMissense: likely pathogenic (0.7559); Very rare (popmax 0.00432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Lys68Thr (c.203A>C)?

ABCC2 p.Lys68Thr (c.203A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Lys68Thr (c.203A>C) in the general population?

ABCC2 p.Lys68Thr (c.203A>C) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about ABCC2 p.Lys68Thr (c.203A>C)?

AlphaMissense predicts likely pathogenic (score 0.7559) — an in-silico prediction, not a clinical call.

ABCC2 p.Lys68Thr

c.203A>C · rs375805189 · VCV1085824

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7559 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7559	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	25.0	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 0.00432% European (non-Finnish) · 51/1,179,986 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00353% 57/1,613,982 alleles · very rare exomes 48/1,461,838 · genomes 9/152,144 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)grpmax	0.00432%	23,137
Finnishnot grpmax-eligible	0.00312%	32,014
Admixed American	0.00167%	60,004

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys68Thr
Coding: c.203A>C
MANE Select: NM_000392
dbSNP: rs375805189
Type: single nucleotide variant
Location: chr10:99784777 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 68: 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.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-lys68thr (accessed [today's date]).

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