Is ABCC2 p.Thr30Ser (c.88A>T) pathogenic?

ABCC2 p.Thr30Ser (c.88A>T) is classified Uncertain significance in ABCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: ambiguous (0.5383); Ultra-rare (popmax 0.04%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCC2 p.Thr30Ser (c.88A>T)?

ABCC2 p.Thr30Ser (c.88A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC2 p.Thr30Ser (c.88A>T) in the general population?

ABCC2 p.Thr30Ser (c.88A>T) is ultra-rare (popmax 0.04%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Thr30Ser (c.88A>T)?

AlphaMissense predicts ambiguous (score 0.5383) — an in-silico prediction, not a clinical call.

ABCC2 p.Thr30Ser

c.88A>T · rs562413451 · VCV3128077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5383 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5383	ambiguous
REVEL	0.446	indeterminate
SaProt	LLR -9.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	25.7	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 0.04% Admixed American · 24/60,020 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.00167% 27/1,614,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,501
Remaining individualsnot grpmax-eligible	0.0048%	20,836

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.Thr30Ser
Coding: c.88A>T
MANE Select: NM_000392
dbSNP: rs562413451
Type: single nucleotide variant
Location: chr10:99784662 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 30: 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.Thr30= 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-thr30ser (accessed [today's date]).

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