Is NLRP7 p.Pro33= (c.99C>T) pathogenic?

NLRP7 p.Pro33= (c.99C>T) is classified Uncertain significance in NLRP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Rare (popmax 0.132%, mid); Associated with hydatidiform mole, recurrent, 1.

What condition is associated with NLRP7 p.Pro33= (c.99C>T)?

NLRP7 p.Pro33= (c.99C>T) is associated with hydatidiform mole, recurrent, 1 (ClinVar).

How common is NLRP7 p.Pro33= (c.99C>T) in the general population?

NLRP7 p.Pro33= (c.99C>T) is rare (popmax 0.132%, mid) (gnomAD).

NLRP7 p.Pro33=

c.99C>T · rs145372368 · VCV893671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.132%, 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 -5.1	GERP 1.9
Overall
CADD	3.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00502% 81/1,614,036 alleles · rare exomes 73/1,461,884 · genomes 8/152,152 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
South Asian	0.0121%	8,280
European (non-Finnish)	0.00466%	21,455
African / African-American	0.004%	24,997
Admixed American	0.00334%	29,984
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Pro33=
Coding: c.99C>T
MANE Select: NM_001127255
dbSNP: rs145372368
Type: single nucleotide variant
Location: chr19:54941613 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.25 · 3 PDB
Residue 33: 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.Pro33Leu 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-pro33 (accessed [today's date]).

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