Is NLRP7 p.Ser3= (c.9G>A) pathogenic?

NLRP7 p.Ser3= (c.9G>A) is classified Uncertain significance in NLRP7 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-12). Ultra-rare (popmax 0.0496%, mid); Associated with hydatidiform mole, recurrent, 1.

What condition is associated with NLRP7 p.Ser3= (c.9G>A)?

NLRP7 p.Ser3= (c.9G>A) is associated with hydatidiform mole, recurrent, 1 (ClinVar).

How common is NLRP7 p.Ser3= (c.9G>A) in the general population?

NLRP7 p.Ser3= (c.9G>A) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

NLRP7 p.Ser3=

c.9G>A · rs199475821 · VCV127264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Conditions

hydatidiform mole, recurrent, 1

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	GERP -6.5
Overall
CADD	1.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0496% Middle Eastern · 3/6,054 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00155% 25/1,612,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,018
Remaining individualsnot grpmax-eligible	0.00641%	15,605
African / African-American	0.00401%	24,959
European (non-Finnish)	0.00119%	84,212
South Asian	0.0011%	90,914

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: NLRP7
Protein: p.Ser3=
Coding: c.9G>A
MANE Select: NM_001127255
dbSNP: rs199475821
Type: single nucleotide variant
Location: chr19:54941703 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.25 · 3 PDB
Residue 3: the pyrin domain

Full NLRP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hydatidiform mole, recurrent, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NLRP7 p.Ser3Leu Uncertain significance ★ ⚠ same residue
NLRP7 c.352+13G>A Uncertain significance ★★ same condition
NLRP7 c.-9C>T Uncertain significance ★★ same condition
NLRP7 p.Arg390Cys Uncertain significance ★★ ⚠ same condition
NLRP7 p.Arg390His Uncertain significance ★★ ⚠ same condition
NLRP7 p.Asn930Tyr Uncertain significance ★★ ⚠ same condition
NLRP7 p.Cys270Tyr Uncertain significance ★★ ⚠ same condition
NLRP7 p.Cys399Tyr 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/nlrp7-p-ser3 (accessed [today's date]).

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