Is NLRP7 p.Ser669Cys (c.2006C>G) pathogenic?

NLRP7 p.Ser669Cys (c.2006C>G) is classified Uncertain significance in NLRP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-22). AlphaMissense: likely benign (0.1146); Very rare (popmax 0.00334%, amr); Associated with hydatidiform mole, recurrent, 1.

What condition is associated with NLRP7 p.Ser669Cys (c.2006C>G)?

NLRP7 p.Ser669Cys (c.2006C>G) is associated with hydatidiform mole, recurrent, 1 (ClinVar).

How common is NLRP7 p.Ser669Cys (c.2006C>G) in the general population?

NLRP7 p.Ser669Cys (c.2006C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about NLRP7 p.Ser669Cys (c.2006C>G)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

NLRP7 p.Ser669Cys

c.2006C>G · VCV4079439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hydatidiform mole, recurrent, 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP 3.7, phastCons 0.009
Overall
CADD	19.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,946 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,990 alleles · very rare exomes 3/1,461,876 · genomes 2/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,973
European (non-Finnish)	0.000254%	393,343

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.Ser669Cys
Coding: c.2006C>G
MANE Select: NM_001127255
Type: single nucleotide variant
Location: chr19:54938167 (GRCh38)

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

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-ser669cys (accessed [today's date]).

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