Is SKIC2 p.Pro44= (c.132C>T) pathogenic?

SKIC2 p.Pro44= (c.132C>T) is classified Conflicting classifications of pathogenicity in SKIC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-26). Absent from gnomAD v4.1; Associated with trichohepatoenteric syndrome 2.

What condition is associated with SKIC2 p.Pro44= (c.132C>T)?

SKIC2 p.Pro44= (c.132C>T) is associated with trichohepatoenteric syndrome 2 (ClinVar).

How common is SKIC2 p.Pro44= (c.132C>T) in the general population?

SKIC2 p.Pro44= (c.132C>T) is absent from gnomAD v4.1 (gnomAD).

How is Trichohepatoenteric syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SKIC2 p.Pro44=

c.132C>T · rs886061306 · VCV356311

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

trichohepatoenteric syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.028	GERP -0.86, phastCons 0.81
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SKIC2
Protein: p.Pro44=
Coding: c.132C>T
MANE Select: NM_006929
dbSNP: rs886061306
Type: single nucleotide variant
Location: chr6:31960015 (GRCh38)
Structure: AlphaFold pLDDT 81.32 · 11 PDB

Full SKIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

trichohepatoenteric syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Trichohepatoenteric syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

SKIC2 p.Pro44Ser Uncertain significance ★ ⚠ same residue
SKIC2 c.1404-2A>G Pathogenic/Likely pathogenic ★★ same condition
SKIC2 c.2203-1G>A Pathogenic/Likely pathogenic ★★ same condition
SKIC2 c.2341-1G>T Pathogenic/Likely pathogenic ★★ same condition
SKIC2 c.2341-2A>G Pathogenic/Likely pathogenic ★★ same condition
SKIC2 c.470-1G>A Likely pathogenic ★★ same condition
SKIC2 p.Arg1063Ter Pathogenic ★★ same condition
SKIC2 p.Arg253Ter Pathogenic/Likely pathogenic ★★ 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/skic2-p-pro44 (accessed [today's date]).

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