Is MYL2 p.Pro95= (c.285T>G) pathogenic?

MYL2 p.Pro95= (c.285T>G) is classified Likely benign in MYL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-30). Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with MYL2 p.Pro95= (c.285T>G)?

MYL2 p.Pro95= (c.285T>G) is associated with cardiomyopathy, hypertrophic cardiomyopathy 10 (ClinVar).

How common is MYL2 p.Pro95= (c.285T>G) in the general population?

MYL2 p.Pro95= (c.285T>G) is absent from gnomAD v4.1 (gnomAD).

MYL2 p.Pro95=

c.285T>G · rs1592799785 · VCV1082198

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiomyopathy

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 -8.3	GERP -5.4
Overall
CADD	0.199	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: MYL2
Protein: p.Pro95=
Coding: c.285T>G
MANE Select: NM_000432
dbSNP: rs1592799785
Type: single nucleotide variant
Location: chr12:110913314 (GRCh38)
Gene constraint: LOEUF 1.157 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 6 PDB
Residue 95: a UniProt-annotated variant site (in cmh10; with mid-left ventricular chamber thickening; decrease calcium binding affinity); the ef-hand 2 domain

Full MYL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: hypertrophic cardiomyopathy 10

Similar variants

MYL2 p.Pro95Ala Uncertain significance ★★ ⚠ same residue
MYL2 p.Pro95Ser Uncertain significance ★★ same residue
MYL2 p.Pro95Leu Uncertain significance ★ ⚠ same residue
MYL2 p.Pro95Thr Uncertain significance ★ ⚠ same residue
MYL2 p.Gly162Glu Likely pathogenic ★★★ ⚠ same condition
MYL2 p.Gln126Glu Uncertain significance ★★★ ⚠ same condition
MYL2 p.Gly162Arg Uncertain significance ★★★ ⚠ same condition
MYL2 p.Gly57Glu 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/myl2-p-pro95 (accessed [today's date]).

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