Is NLRP14 p.Val441Met (c.1321G>A) pathogenic?

NLRP14 p.Val441Met (c.1321G>A) is classified Likely benign in NLRP14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-19). AlphaMissense: likely benign (0.2045); Low-frequency (popmax 1.52%, afr); Associated with NLRP14-related disorder.

What condition is associated with NLRP14 p.Val441Met (c.1321G>A)?

NLRP14 p.Val441Met (c.1321G>A) is associated with NLRP14-related disorder (ClinVar).

How common is NLRP14 p.Val441Met (c.1321G>A) in the general population?

NLRP14 p.Val441Met (c.1321G>A) is low-frequency (popmax 1.52%, afr) (gnomAD).

What do computational predictors say about NLRP14 p.Val441Met (c.1321G>A)?

AlphaMissense predicts likely benign (score 0.2045) — an in-silico prediction, not a clinical call.

NLRP14 p.Val441Met

c.1321G>A · rs147389856 · VCV3033102

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2045 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

NLRP14-related disorder

Computational evidence

Protein change
AlphaMissense	0.2045	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.92, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	22.3	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 1.52% African / African-American · 1,140/75,048 alleles

Filtering AF 1.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.42%

Overall 0.0866% 1,398/1,614,168 alleles · low-frequency exomes 708/1,461,884 · genomes 690/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.52%	66
Ashkenazi Jewishnot grpmax-eligible	0.223%	449
Admixed American	0.112%	896
Remaining individualsnot grpmax-eligible	0.11%	906
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.00424%	23,600
South Asian	0.0011%	91,082

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.Val441Met
Coding: c.1321G>A
MANE Select: NM_176822
dbSNP: rs147389856
Type: single nucleotide variant
Location: chr11:7043347 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 441: the nacht domain; a UniProt-annotated variant site (in)

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

Disease context

NLRP14-related disorder

Similar variants

NLRP14 c.1958+6T>C Likely benign same condition
NLRP14 p.Ala432= Benign same condition
NLRP14 p.Asp12= Likely benign same condition
NLRP14 p.Asp3Gly Benign same condition
NLRP14 p.Cys750Tyr Likely benign same condition
NLRP14 p.Gln484= Likely benign same condition
NLRP14 p.Glu21Lys Likely benign same condition
NLRP14 p.Gly242Asp Benign 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/nlrp14-p-val441met (accessed [today's date]).

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