Is CTRC p.Arg29Leu (c.86G>T) pathogenic?

CTRC p.Arg29Leu (c.86G>T) is classified Uncertain significance in CTRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-29). AlphaMissense: likely pathogenic (0.6826); Very rare (popmax 6.91e-05%); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Arg29Leu (c.86G>T)?

CTRC p.Arg29Leu (c.86G>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Arg29Leu (c.86G>T) in the general population?

CTRC p.Arg29Leu (c.86G>T) is very rare (popmax 6.91e-05%) (gnomAD).

What do computational predictors say about CTRC p.Arg29Leu (c.86G>T)?

AlphaMissense predicts likely pathogenic (score 0.6826) — an in-silico prediction, not a clinical call.

CTRC p.Arg29Leu

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.86G>T · rs772024986 · VCV1163624

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.91e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.6826	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -11.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.91e-05%

Overall 6.91e-05% 1/1,446,834 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: CTRC
Protein: p.Arg29Leu
Coding: c.86G>T
MANE Select: NM_007272
dbSNP: rs772024986
Type: single nucleotide variant
Location: chr1:15440345 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 29: a disulfide bond; a UniProt-annotated variant site (found in patients with chronic pancreatitis; uncertain significance)

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.Arg29Ter Pathogenic/Likely pathogenic ★★ same residue
CTRC p.Arg29Gln Uncertain significance ★★ ⚠ same residue
CTRC p.Arg29Pro Uncertain significance ★ ⚠ same residue
CTRC p.Arg29= Likely benign ★ same residue
CTRC c.494-1G>C 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-arg29leu (accessed [today's date]).

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