Is MYPN p.Pro396= (c.1188A>G) pathogenic?

MYPN p.Pro396= (c.1188A>G) is classified Likely benign in MYPN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-27). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MYPN p.Pro396= (c.1188A>G)?

MYPN p.Pro396= (c.1188A>G) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1KK (ClinVar).

How common is MYPN p.Pro396= (c.1188A>G) in the general population?

MYPN p.Pro396= (c.1188A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

MYPN p.Pro396=

c.1188A>G · rs371437119 · VCV227713

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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 0.88	phastCons 0.98
Overall
CADD	7.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,950 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,076 alleles · very rare exomes 1/1,461,832 · genomes 1/152,244 · joint denominator

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.Pro396=
Coding: c.1188A>G
MANE Select: NM_032578
dbSNP: rs371437119
Type: single nucleotide variant
Location: chr10:68148410 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.71
Residue 396: the 'interaction with carp' region

Full MYPN 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: dilated cardiomyopathy 1KK

Similar variants

MYPN p.Pro396Ala Uncertain significance ★ ⚠ 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-pro396 (accessed [today's date]).

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