Is ABCB11 p.Pro447Ser (c.1339C>T) pathogenic?

ABCB11 p.Pro447Ser (c.1339C>T) is classified Benign in ABCB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.076); Very rare (popmax 0.00446%, eas).

How common is ABCB11 p.Pro447Ser (c.1339C>T) in the general population?

ABCB11 p.Pro447Ser (c.1339C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ABCB11 p.Pro447Ser (c.1339C>T)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

ABCB11 p.Pro447Ser

c.1339C>T · rs773299323 · VCV2165857

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -4.2, phastCons 0.84
Overall
CADD	13.19	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 0.00446% East Asian · 2/44,802 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000137% 2/1,460,020 alleles · very rare

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: ABCB11
Protein: p.Pro447Ser
Coding: c.1339C>T
MANE Select: NM_003742
dbSNP: rs773299323
Type: single nucleotide variant
Location: chr2:168973810 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.23 · 9 PDB
Residue 447: the abc transporter 1 domain

Full ABCB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB11 p.Pro447Leu Uncertain significance ★ ⚠ same residue
ABCB11 p.Pro447= Likely benign ★ same residue
ABCB11 c.1084-2A>G Pathogenic ★★ same type
ABCB11 c.1197+1G>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-1G>C Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.1198-2A>C Likely pathogenic ★★ same type
ABCB11 c.1435-2A>T Pathogenic/Likely pathogenic ★★ same type
ABCB11 c.150+1G>A Pathogenic/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/abcb11-p-pro447ser (accessed [today's date]).

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