Is CALR3 p.Pro260= (c.780G>T) pathogenic?

CALR3 p.Pro260= (c.780G>T) is classified Likely benign in CALR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-15). Very rare (popmax 0.000169%, nfe); Associated with hypertrophic cardiomyopathy 19.

What condition is associated with CALR3 p.Pro260= (c.780G>T)?

CALR3 p.Pro260= (c.780G>T) is associated with hypertrophic cardiomyopathy 19 (ClinVar).

How common is CALR3 p.Pro260= (c.780G>T) in the general population?

CALR3 p.Pro260= (c.780G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

CALR3 p.Pro260=

c.780G>T · rs775009764 · VCV241952

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

hypertrophic cardiomyopathy 19

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,868 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: CALR3
Protein: p.Pro260=
Coding: c.780G>T
MANE Select: NM_145046
dbSNP: rs775009764
Type: single nucleotide variant
Location: chr19:16482684 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.43
Residue 260: the 'p-domain' region; the '3 x approximate repeats' region

Full CALR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertrophic cardiomyopathy 19 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CALR3 p.Pro260Leu Uncertain significance ★★ ⚠ same residue
CALR3 p.Ala331Val Uncertain significance ★★ ⚠ same condition
CALR3 p.Ala348Val Uncertain significance ★★ ⚠ same condition
CALR3 p.Arg278Cys Uncertain significance ★★ ⚠ same condition
CALR3 p.Arg278His Uncertain significance ★★ ⚠ same condition
CALR3 p.Arg278Leu Uncertain significance ★★ ⚠ same condition
CALR3 p.Arg308Ile Uncertain significance ★★ ⚠ same condition
CALR3 p.Arg80Cys 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/calr3-p-pro260 (accessed [today's date]).

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