Is MYPN p.Arg1069= (c.3207C>T) pathogenic?

MYPN p.Arg1069= (c.3207C>T) is classified Likely benign in MYPN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Very rare (popmax 0.00133%, afr); Associated with dilated cardiomyopathy 1KK.

What condition is associated with MYPN p.Arg1069= (c.3207C>T)?

MYPN p.Arg1069= (c.3207C>T) is associated with dilated cardiomyopathy 1KK (ClinVar).

How common is MYPN p.Arg1069= (c.3207C>T) in the general population?

MYPN p.Arg1069= (c.3207C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MYPN p.Arg1069=

c.3207C>T · rs766738381 · VCV2171594

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

dilated cardiomyopathy 1KK

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 -0.015	GERP -3.6, phastCons 0.72
Overall
CADD	8.292	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,908 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,868 alleles · very rare exomes 4/1,461,720 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,908
European (non-Finnish)	0.000339%	294,985

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: MYPN
Protein: p.Arg1069=
Coding: c.3207C>T
MANE Select: NM_032578
dbSNP: rs766738381
Type: single nucleotide variant
Location: chr10:68197400 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.71
Residue 1069: the 'interaction with actn' region

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

Disease context

dilated cardiomyopathy 1KK — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYPN p.Arg1069Cys Uncertain significance ★★ ⚠ same residue
MYPN p.Arg1069His Uncertain significance ★★ ⚠ same residue
MYPN p.Arg1069Leu Uncertain significance ★ same residue
MYPN p.Arg1069Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MYPN c.1317+1G>A Likely pathogenic ★★ same condition
MYPN p.Arg1072Ter Pathogenic ★★ same condition
MYPN p.Arg489Ter Pathogenic ★★ same condition
MYPN p.Arg996Ter Pathogenic/Likely pathogenic ★★ 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/mypn-p-arg1069 (accessed [today's date]).

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