Is CTRC p.Phe68Ile (c.202T>A) pathogenic?

CTRC p.Phe68Ile (c.202T>A) is classified Uncertain significance in CTRC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-02). AlphaMissense: ambiguous (0.4809); Ultra-rare (popmax 0.0164%, mid); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Phe68Ile (c.202T>A)?

CTRC p.Phe68Ile (c.202T>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Phe68Ile (c.202T>A) in the general population?

CTRC p.Phe68Ile (c.202T>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CTRC p.Phe68Ile (c.202T>A)?

AlphaMissense predicts ambiguous (score 0.4809) — an in-silico prediction, not a clinical call.

CTRC p.Phe68Ile

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.202T>A · rs772513025 · VCV618057

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4809 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.4809	ambiguous
REVEL	0.349	indeterminate
SaProt	LLR -9.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -4.5
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	17.32	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00421% 68/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00542%	18,438
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,926

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.Phe68Ile
Coding: c.202T>A
MANE Select: NM_007272
dbSNP: rs772513025
Type: single nucleotide variant
Location: chr1:15440562 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 68: 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.Phe68= Likely benign ★★ same residue
CTRC p.Phe68Ser 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-phe68ile (accessed [today's date]).

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