Is MYPN p.Ser836Phe (c.2507C>T) pathogenic?

MYPN p.Ser836Phe (c.2507C>T) is classified Uncertain significance in MYPN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-13). AlphaMissense: ambiguous (0.507); Ultra-rare (popmax 0.02%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MYPN p.Ser836Phe (c.2507C>T)?

MYPN p.Ser836Phe (c.2507C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1KK (ClinVar).

How common is MYPN p.Ser836Phe (c.2507C>T) in the general population?

MYPN p.Ser836Phe (c.2507C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about MYPN p.Ser836Phe (c.2507C>T)?

AlphaMissense predicts ambiguous (score 0.507) — an in-silico prediction, not a clinical call.

MYPN p.Ser836Phe

c.2507C>T · rs376141715 · VCV582151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.507 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.507	ambiguous
REVEL	0.46	indeterminate
SaProt	LLR -8.93	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 89 kb · p 0.33 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/75,054 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00987%

Overall 0.0013% 21/1,614,212 alleles · ultra-rare exomes 10/1,461,880 · genomes 11/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,004
Admixed American	0.01%	10,003

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.Ser836Phe
Coding: c.2507C>T
MANE Select: NM_032578
dbSNP: rs376141715
Type: single nucleotide variant
Location: chr10:68174599 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.71

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-ser836phe (accessed [today's date]).

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