Is MYPN p.Pro625= (c.1875C>T) pathogenic?

MYPN p.Pro625= (c.1875C>T) is classified Benign in MYPN (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with MYPN p.Pro625= (c.1875C>T)?

MYPN p.Pro625= (c.1875C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1KK (ClinVar).

MYPN p.Pro625=

Q: How common is MYPN p.Pro625= (c.1875C>T) in the general population?

MYPN p.Pro625= (c.1875C>T) is common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1875C>T · rs2673793 · VCV31796

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele

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 -9	GERP -5.4
Overall
CADD	0.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.8% Admixed American · 14,262/59,984 alleles

Filtering AF 23.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.3%

Overall 17.7% 285,881/1,613,890 alleles · common exomes 259,468/1,461,812 · genomes 26,413/152,078 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	31.3%	3
Admixed Americangrpmax	23.8%	4
Middle Eastern	22.6%	4
Finnishnot grpmax-eligible	19.7%	5
South Asian	19.2%	5
Remaining individualsnot grpmax-eligible	18%	6
European (non-Finnish)	17.3%	6
African / African-American	15.5%	6
Amishnot grpmax-eligible	12.7%	8
East Asian	9.27%	11

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro625=
Coding: c.1875C>T
MANE Select: NM_032578
dbSNP: rs2673793
Type: single nucleotide variant
Location: chr10:68166568 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.71
Residue 625: the 'disordered' 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 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
MYPN c.3159-3T>C 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-pro625 (accessed [today's date]).

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