Is CALR3 p.Tyr129= (c.387T>C) pathogenic?

CALR3 p.Tyr129= (c.387T>C) is classified Likely benign in CALR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy 19.

What condition is associated with CALR3 p.Tyr129= (c.387T>C)?

CALR3 p.Tyr129= (c.387T>C) is associated with hypertrophic cardiomyopathy 19 (ClinVar).

How common is CALR3 p.Tyr129= (c.387T>C) in the general population?

CALR3 p.Tyr129= (c.387T>C) is absent from gnomAD v4.1 (gnomAD).

CALR3 p.Tyr129=

c.387T>C · rs2122142562 · VCV1605565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.027	GERP -4.3, phastCons 0.09
Overall
CADD	4.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CALR3
Protein: p.Tyr129=
Coding: c.387T>C
MANE Select: NM_145046
dbSNP: rs2122142562
Type: single nucleotide variant
Location: chr19:16490377 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.43
Residue 129: a disulfide bond; the 'n-domain' 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.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
CALR3 p.Asp242His 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-tyr129 (accessed [today's date]).

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