Is NLRP14 p.Leu897Pro (c.2690T>C) pathogenic?

NLRP14 p.Leu897Pro (c.2690T>C) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely benign (0.2026); Ultra-rare (popmax 0.0165%, mid).

How common is NLRP14 p.Leu897Pro (c.2690T>C) in the general population?

NLRP14 p.Leu897Pro (c.2690T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about NLRP14 p.Leu897Pro (c.2690T>C)?

AlphaMissense predicts likely benign (score 0.2026) — an in-silico prediction, not a clinical call.

NLRP14 p.Leu897Pro

c.2690T>C · rs768724978 · VCV2458206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2026 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2026	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -11.75	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.74	GERP -2.6
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	15.95	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.0018% 29/1,612,642 alleles · ultra-rare exomes 24/1,460,658 · genomes 5/151,984 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
Remaining individualsnot grpmax-eligible	0.0144%	6,934
Admixed American	0.00501%	19,961
African / African-American	0.00134%	74,848
European (non-Finnish)	0.00127%	78,599

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: NLRP14
Protein: p.Leu897Pro
Coding: c.2690T>C
MANE Select: NM_176822
dbSNP: rs768724978
Type: single nucleotide variant
Location: chr11:7059950 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB

Full NLRP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RBMXL2 p.Asp128Val Uncertain significance ★★ ⚠ same type
NLRP14 c.1958+74C>A Benign ★★ same type
NLRP14 c.2124-36G>A Benign ★★ same type
NLRP14 c.2292-104A>C Benign ★★ same type
NLRP14 c.3146+85C>A Benign ★★ same type
NLRP14 c.361+46T>G Benign ★★ same type
NLRP14 c.-21-48T>A Benign ★★ same type
NLRP14 p.Ala432Ser Benign ★★ same type

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/nlrp14-p-leu897pro (accessed [today's date]).

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