Is ABCB4 p.Pro1088Ser (c.3262C>T) pathogenic?

ABCB4 p.Pro1088Ser (c.3262C>T) is classified Uncertain significance in ABCB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: ambiguous (0.3786); Very rare (popmax 0.00659%, sas); Associated with Inborn genetic diseases.

What condition is associated with ABCB4 p.Pro1088Ser (c.3262C>T)?

ABCB4 p.Pro1088Ser (c.3262C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB4 p.Pro1088Ser (c.3262C>T) in the general population?

ABCB4 p.Pro1088Ser (c.3262C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ABCB4 p.Pro1088Ser (c.3262C>T)?

AlphaMissense predicts ambiguous (score 0.3786) — an in-silico prediction, not a clinical call.

ABCB4 p.Pro1088Ser

c.3262C>T · rs774536983 · VCV3121320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3786	ambiguous
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 14 kb · p 8.2e-06 · regional, not allelic
Overall
CADD	24.2	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 0.00659% South Asian · 6/91,078 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000434% 7/1,613,814 alleles · very rare exomes 6/1,461,640 · genomes 1/152,174 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
East Asian	0.00223%	44,898

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: ABCB4
Protein: p.Pro1088Ser
Coding: c.3262C>T
MANE Select: NM_000443
dbSNP: rs774536983
Type: single nucleotide variant
Location: chr7:87408054 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 83.36 · 4 PDB
Residue 1088: the abc transporter 2 domain

Full ABCB4 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

ABCB4 p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala304Ser Uncertain significance ★★ ⚠ same condition
ABCB4 p.Ala333Thr Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg159Gln Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg661His Uncertain significance ★★ ⚠ same condition
ABCB4 p.Arg969Cys Uncertain significance ★★ ⚠ same condition
ABCB4 p.Cys1226Gly Uncertain significance ★★ ⚠ same condition
ABCB4 p.Cys955Gly 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/abcb4-p-pro1088ser (accessed [today's date]).

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