Is CTRC p.Ser239Cys (c.716C>G) pathogenic?

CTRC p.Ser239Cys (c.716C>G) is classified Conflicting classifications of pathogenicity in CTRC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-22). AlphaMissense: likely pathogenic (0.8248); Very rare (popmax 6.84e-05%); Associated with CTRC-related disorder.

What condition is associated with CTRC p.Ser239Cys (c.716C>G)?

CTRC p.Ser239Cys (c.716C>G) is associated with CTRC-related disorder, hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Ser239Cys (c.716C>G) in the general population?

CTRC p.Ser239Cys (c.716C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CTRC p.Ser239Cys (c.716C>G)?

AlphaMissense predicts likely pathogenic (score 0.8248) — an in-silico prediction, not a clinical call.

CTRC p.Ser239Cys

c.716C>G · VCV3720160

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CTRC-related disorder

Computational evidence

Protein change
AlphaMissense	0.8248	likely pathogenic
REVEL	0.772	pathogenic-leaning
SaProt	LLR -14.98	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 5.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,882 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.Ser239Cys
Coding: c.716C>G
MANE Select: NM_007272
Type: single nucleotide variant
Location: chr1:15445673 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 239: a disulfide bond; the peptidase s1 domain; a UniProt-annotated variant site (found in patients with chronic pancreatitis; uncertain significance); a β-strand

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

Disease context

CTRC-related disorder

Also linked: hereditary chronic pancreatitis

Similar variants

CTRC p.Ser239Phe Uncertain significance ★★ ⚠ same residue
CTRC p.Ser239= Likely benign ★ 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-ser239cys (accessed [today's date]).

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