Is NPPA p.Ser129= (c.387C>T) pathogenic?

NPPA p.Ser129= (c.387C>T) is classified Likely benign in NPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-13). Ultra-rare (popmax 0.0121%, afr); Associated with atrial fibrillation, familial, 6.

What condition is associated with NPPA p.Ser129= (c.387C>T)?

NPPA p.Ser129= (c.387C>T) is associated with atrial fibrillation, familial, 6 (ClinVar).

How common is NPPA p.Ser129= (c.387C>T) in the general population?

NPPA p.Ser129= (c.387C>T) is ultra-rare (popmax 0.0121%, afr) (gnomAD).

How is Hereditary atrial fibrillation inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

NPPA p.Ser129=

c.387C>T · rs372868878 · VCV2917042

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, afr)

Conditions

atrial fibrillation, familial, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.5	GERP -1.9, phastCons 1
Overall
CADD	7.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% African / African-American · 9/74,312 alleles

Filtering AF 0.00628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00471%

Overall 0.000565% 9/1,593,376 alleles · ultra-rare

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: NPPA
Protein: p.Ser129=
Coding: c.387C>T
dbSNP: rs372868878
Type: single nucleotide variant
Location: chr1:11847176 (GRCh38)

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

Disease context

atrial fibrillation, familial, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary atrial fibrillation (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

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/nppa-p-ser129 (accessed [today's date]).

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