Is CTRC p.Thr62Ser (c.185C>G) pathogenic?

CTRC p.Thr62Ser (c.185C>G) is classified Uncertain significance in CTRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-25). AlphaMissense: likely benign (0.2466); Very rare (popmax 0.00167%, amr); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Thr62Ser (c.185C>G)?

CTRC p.Thr62Ser (c.185C>G) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Thr62Ser (c.185C>G) in the general population?

CTRC p.Thr62Ser (c.185C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CTRC p.Thr62Ser (c.185C>G)?

AlphaMissense predicts likely benign (score 0.2466) — an in-silico prediction, not a clinical call.

CTRC p.Thr62Ser

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.185C>G · rs774966069 · VCV1163625

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.2466	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -2.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	13.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	0.000508%	196,670

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.Thr62Ser
Coding: c.185C>G
MANE Select: NM_007272
dbSNP: rs774966069
Type: single nucleotide variant
Location: chr1:15440545 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 62: a disulfide bond; the peptidase s1 domain; a β-strand

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.Thr62Ile 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
CTRC p.Ala12Val 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-thr62ser (accessed [today's date]).

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