Is MYOZ2 p.Pro168= (c.504T>C) pathogenic?

MYOZ2 p.Pro168= (c.504T>C) is classified Likely benign in MYOZ2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). Very rare (popmax 0.004%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MYOZ2 p.Pro168= (c.504T>C)?

MYOZ2 p.Pro168= (c.504T>C) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is MYOZ2 p.Pro168= (c.504T>C) in the general population?

MYOZ2 p.Pro168= (c.504T>C) is very rare (popmax 0.004%, afr) (gnomAD).

MYOZ2 p.Pro168=

c.504T>C · rs769668877 · VCV227712

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Cardiovascular phenotype

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 -3.3	GERP -3.8
Overall
CADD	4.403	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,970 alleles · very rare exomes 1/1,461,800 · genomes 3/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
Admixed American	0.00167%	60,000

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: MYOZ2
Protein: p.Pro168=
Coding: c.504T>C
MANE Select: NM_016599
dbSNP: rs769668877
Type: single nucleotide variant
Location: chr4:119164338 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.51

Full MYOZ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy

Similar variants

MYOZ2 c.246+4G>A Uncertain significance ★★ same condition
MYOZ2 c.376+2T>C Uncertain significance ★★ same condition
MYOZ2 c.560+2T>C Uncertain significance ★★ same condition
MYOZ2 c.-3A>G Uncertain significance ★★ same condition
MYOZ2 p.Ala104Val Uncertain significance ★★ ⚠ same condition
MYOZ2 p.Ala189Val Uncertain significance ★★ ⚠ same condition
MYOZ2 p.Arg115Ter Uncertain significance ★★ same condition
MYOZ2 p.Arg183Ser 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/myoz2-p-pro168 (accessed [today's date]).

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