Is CTRC p.Val180= (c.540G>T) pathogenic?

CTRC p.Val180= (c.540G>T) is classified Likely benign in CTRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-19). Ultra-rare (popmax 0.0521%, afr); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Val180= (c.540G>T)?

CTRC p.Val180= (c.540G>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Val180= (c.540G>T) in the general population?

CTRC p.Val180= (c.540G>T) is ultra-rare (popmax 0.0521%, afr) (gnomAD).

CTRC p.Val180=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.540G>T · rs371479067 · VCV1616700

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0521%, afr)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.83	GERP -5.2
Overall
CADD	0.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0521% African / African-American · 39/74,924 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0346%

Overall 0.00372% 60/1,614,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0521%	1,921
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.005%	20,001

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: CTRC
Protein: p.Val180=
Coding: c.540G>T
MANE Select: NM_007272
dbSNP: rs371479067
Type: single nucleotide variant
Location: chr1:15444652 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 180: a disulfide bond; the peptidase s1 domain

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.Val180Met Uncertain significance ★★ ⚠ same residue
CTRC p.Val180Ala Uncertain significance ★ ⚠ same residue
CTRC p.Val180Leu 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

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-val180 (accessed [today's date]).

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