Is MYOZ2 p.Pro112= (c.336A>G) pathogenic?

MYOZ2 p.Pro112= (c.336A>G) is classified Conflicting classifications of pathogenicity in MYOZ2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-04-25). Ultra-rare (popmax 0.0878%, sas); Associated with Cardiovascular phenotype.

What condition is associated with MYOZ2 p.Pro112= (c.336A>G)?

MYOZ2 p.Pro112= (c.336A>G) is associated with Cardiovascular phenotype, cardiomyopathy (ClinVar).

How common is MYOZ2 p.Pro112= (c.336A>G) in the general population?

MYOZ2 p.Pro112= (c.336A>G) is ultra-rare (popmax 0.0878%, sas) (gnomAD).

MYOZ2 p.Pro112=

c.336A>G · rs774333721 · VCV626724

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0878%, sas)

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 -1.7	GERP -3.3
Overall
CADD	3.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0878% South Asian · 80/91,086 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0666%

Overall 0.00508% 82/1,613,972 alleles · ultra-rare exomes 77/1,461,824 · genomes 5/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0878%	1,139
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	8.47e-05%	1,179,988

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.Pro112=
Coding: c.336A>G
MANE Select: NM_016599
dbSNP: rs774333721
Type: single nucleotide variant
Location: chr4:119158111 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.51
Residue 112: the 'disordered' region

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: cardiomyopathy

Similar variants

MYOZ2 c.246+4G>A 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
MYOZ2 p.Arg230Gln 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-pro112 (accessed [today's date]).

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