Is ABCB1 p.Ser2Cys (c.4A>T) pathogenic?

ABCB1 p.Ser2Cys (c.4A>T) is classified Uncertain significance in ABCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Ultra-rare (popmax 0.0196%, amr); Associated with inflammatory bowel disease 13.

What condition is associated with ABCB1 p.Ser2Cys (c.4A>T)?

ABCB1 p.Ser2Cys (c.4A>T) is associated with inflammatory bowel disease 13 (ClinVar).

How common is ABCB1 p.Ser2Cys (c.4A>T) in the general population?

ABCB1 p.Ser2Cys (c.4A>T) is ultra-rare (popmax 0.0196%, amr) (gnomAD).

ABCB1 p.Ser2Cys

c.4A>T · VCV3393332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, amr)

Conditions

inflammatory bowel disease 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -2.6
Overall
CADD	2.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0196% Admixed American · 3/15,274 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00284%

Overall 0.00526% 8/152,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0478%	2,090
Admixed Americangrpmax	0.0196%	5,091
European (non-Finnish)	0.00588%	17,007

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: ABCB1
Protein: p.Ser2Cys
Coding: c.4A>T
MANE Select: NM_001348946 · reported on NM_001348945
Type: single nucleotide variant
Location: chr7:87602983 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.72 · 24 PDB

Full ABCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory bowel disease 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RUNDC3B p.Ala2Val Uncertain significance ★ ⚠ same residue
ABCB1 p.Ser893Ala Benign ★★ same condition
ABCB1 p.Arg1183Cys Uncertain significance ★ ⚠ same condition
ABCB1 p.Arg157Gln Uncertain significance ★ ⚠ same condition
ABCB1 p.Ile160Met Uncertain significance ★ ⚠ same condition
ABCB1 c.287-25G>T Benign ★★ same type
ABCB1 p.Ala1132= Benign/Likely benign ★★ same type
ABCB1 p.Gln1107Pro Benign/Likely benign ★★ 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/abcb1-p-ser2cys (accessed [today's date]).

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