Is SLC10A2 p.Trp186fs (c.556del) pathogenic?

SLC10A2 p.Trp186fs (c.556del) is classified Conflicting classifications of pathogenicity in SLC10A2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-29). Rare (popmax 0.132%, sas); Associated with bile acid malabsorption, primary, 1.

What condition is associated with SLC10A2 p.Trp186fs (c.556del)?

SLC10A2 p.Trp186fs (c.556del) is associated with bile acid malabsorption, primary, 1 (ClinVar).

How common is SLC10A2 p.Trp186fs (c.556del) in the general population?

SLC10A2 p.Trp186fs (c.556del) is rare (popmax 0.132%, sas) (gnomAD).

SLC10A2 p.Trp186fs

c.556del · rs781456338 · VCV2868591

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.132%, sas)

Conditions

bile acid malabsorption, primary, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% South Asian · 120/91,038 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0098% 158/1,611,426 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.132%	759
Middle Eastern	0.0988%	1,012
Remaining individualsnot grpmax-eligible	0.0192%	5,199
European (non-Finnish)	0.0017%	58,891

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: SLC10A2
Protein: p.Trp186fs
Coding: c.556del
MANE Select: NM_000452
dbSNP: rs781456338
Type: Deletion
Location: chr13:103052649 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88

Full SLC10A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bile acid malabsorption, primary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC10A2 p.Trp186Ter Uncertain significance ★★ same residue
SLC10A2 p.Ala116Val Uncertain significance ★★ ⚠ same condition
SLC10A2 p.Arg256Ter Uncertain significance ★★ same condition
SLC10A2 p.Cys105Arg Uncertain significance ★★ ⚠ same condition
SLC10A2 p.Cys144Tyr Uncertain significance ★★ ⚠ same condition
SLC10A2 p.Gly77Glu Uncertain significance ★★ ⚠ same condition
SLC10A2 p.Pro251Leu Uncertain significance ★★ same condition
SLC10A2 p.Ser133Cys 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/slc10a2-p-trp186fs (accessed [today's date]).

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