Is CTRC p.Val84Ala (c.251T>C) pathogenic?

CTRC p.Val84Ala (c.251T>C) is classified Uncertain significance in CTRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-26). AlphaMissense: likely pathogenic (0.6048); Ultra-rare (popmax 0.0784%, amr); Associated with hereditary chronic pancreatitis.

What condition is associated with CTRC p.Val84Ala (c.251T>C)?

CTRC p.Val84Ala (c.251T>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is CTRC p.Val84Ala (c.251T>C) in the general population?

CTRC p.Val84Ala (c.251T>C) is ultra-rare (popmax 0.0784%, amr) (gnomAD).

What do computational predictors say about CTRC p.Val84Ala (c.251T>C)?

AlphaMissense predicts likely pathogenic (score 0.6048) — an in-silico prediction, not a clinical call.

CTRC p.Val84Ala

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.251T>C · rs200369419 · VCV641331

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6048 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0784%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.6048	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,121 bp · p 0.049 · regional, not allelic
Overall
CADD	23.5	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 0.0784% Admixed American · 47/59,976 alleles

Filtering AF 0.0605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00378% 61/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0784%	1,276
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.00533%	18,756
European (non-Finnish)	8.48e-05%	1,179,915

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.Val84Ala
Coding: c.251T>C
MANE Select: NM_007272
dbSNP: rs200369419
Type: single nucleotide variant
Location: chr1:15442467 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 1 PDB
Residue 84: 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 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
CTRC p.Ala184Val 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-val84ala (accessed [today's date]).

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