Is MYPN p.Pro1102= (c.3306G>A) pathogenic?

MYPN p.Pro1102= (c.3306G>A) is classified Conflicting classifications of pathogenicity in MYPN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-26). Very rare (popmax 0.00878%, sas); Associated with dilated cardiomyopathy 1KK.

What condition is associated with MYPN p.Pro1102= (c.3306G>A)?

MYPN p.Pro1102= (c.3306G>A) is associated with dilated cardiomyopathy 1KK (ClinVar).

How common is MYPN p.Pro1102= (c.3306G>A) in the general population?

MYPN p.Pro1102= (c.3306G>A) is very rare (popmax 0.00878%, sas) (gnomAD).

MYPN p.Pro1102=

c.3306G>A · rs771521427 · VCV1010575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

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 -5.1	GERP -5.1
Overall
CADD	1.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00878% South Asian · 8/91,078 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00136% 22/1,613,850 alleles · very rare exomes 20/1,461,756 · genomes 2/152,094 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,385
Admixed American	0.00334%	29,982
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,470
African / African-American	0.00134%	74,888
European (non-Finnish)	0.000763%	131,106

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.Pro1102=
Coding: c.3306G>A
MANE Select: NM_032578
dbSNP: rs771521427
Type: single nucleotide variant
Location: chr10:68199388 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.71
Residue 1102: the 'interaction with actn' region; the ig-like 4 domain

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.Pro1102Leu 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
MYPN c.1130+3A>C Uncertain significance ★★ same condition
MYPN c.1974-3C>T Uncertain significance ★★ same condition
MYPN c.3158+6G>T 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/mypn-p-pro1102 (accessed [today's date]).

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