Is CTRC p.Asp121= (c.363T>C) pathogenic?

CTRC p.Asp121= (c.363T>C) is classified Likely benign in CTRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-15). Absent from gnomAD v4.1; Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Asp121= (c.363T>C)?

CTRC p.Asp121= (c.363T>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Asp121= (c.363T>C) in the general population?

CTRC p.Asp121= (c.363T>C) is absent from gnomAD v4.1 (gnomAD).

CTRC p.Asp121=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.363T>C · rs2526296989 · VCV1733501

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.175	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 1.5, phastCons 1
Overall
CADD	11.54	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: CTRC
Protein: p.Asp121=
Coding: c.363T>C
MANE Select: NM_007272
dbSNP: rs2526296989
Type: single nucleotide variant
Location: chr1:15443425 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 121: a disulfide bond; the peptidase s1 domain; an active site

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

Disease context

hereditary chronic pancreatitis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant hereditary chronic pancreatitis (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood
Prevalence: 1-9 / 1 000 000 (France)

Similar variants

CTRC p.Asp121Gly Uncertain significance ★★ ⚠ same residue
CTRC p.Asp121Tyr Uncertain significance ★ same residue
CTRC c.494-1G>C Pathogenic/Likely pathogenic ★★ same condition
CTRC p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
CTRC p.Gln174Ter Pathogenic/Likely pathogenic ★★ same condition
CTRC c.356+1G>A Uncertain significance ★★ same condition
CTRC c.40+4A>G Uncertain significance ★★ same condition
CTRC c.40+6C>T 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/ctrc-p-asp121 (accessed [today's date]).

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