Is NLRP14 p.Phe342Leu (c.1026T>A) pathogenic?

NLRP14 p.Phe342Leu (c.1026T>A) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely pathogenic (0.7655); Very rare (popmax 0.00446%, eas).

How common is NLRP14 p.Phe342Leu (c.1026T>A) in the general population?

NLRP14 p.Phe342Leu (c.1026T>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about NLRP14 p.Phe342Leu (c.1026T>A)?

AlphaMissense predicts likely pathogenic (score 0.7655) — an in-silico prediction, not a clinical call.

NLRP14 p.Phe342Leu

c.1026T>A · VCV3406126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7655	likely pathogenic · top 5% in NLRP14
REVEL	0.159	moderately benign-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.074	GERP -4, phastCons 0.3
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	12.2	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 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,150 alleles · very rare exomes 2/1,461,858 · genomes 0/152,292 · joint denominator

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.Phe342Leu
Coding: c.1026T>A
MANE Select: NM_176822
Type: single nucleotide variant
Location: chr11:7043052 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 342: the nacht domain

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

Similar variants

RBMXL2 p.Arg342Gln Uncertain significance ★ ⚠ same residue
RBMXL2 p.Arg342Trp Uncertain significance ★ ⚠ same residue
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

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-phe342leu (accessed [today's date]).

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