Is NLRP14 p.Lys92Arg (c.275A>G) pathogenic?

NLRP14 p.Lys92Arg (c.275A>G) is classified Benign in NLRP14 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-11-12). AlphaMissense: likely benign (0.0734); Common (popmax 20.7%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about NLRP14 p.Lys92Arg (c.275A>G)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

NLRP14 p.Lys92Arg

Q: How common is NLRP14 p.Lys92Arg (c.275A>G) in the general population?

NLRP14 p.Lys92Arg (c.275A>G) is common (popmax 20.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.275A>G · rs16921697 · VCV1241370

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -2.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -1.7
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	12.3	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 20.7% East Asian · 9,271/44,848 alleles

Filtering AF 20.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.2%

Overall 4.29% 69,137/1,613,208 alleles · common exomes 63,211/1,460,956 · genomes 5,926/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	20.7%	5
South Asian	11.6%	9
Admixed American	8.2%	12
Middle Eastern	5.72%	17
Finnishnot grpmax-eligible	5.23%	19
Remaining individualsnot grpmax-eligible	5.05%	20
European (non-Finnish)	3.07%	33
Ashkenazi Jewishnot grpmax-eligible	2.61%	38
Amishnot grpmax-eligible	1.54%	65
African / African-American	0.844%	119

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.Lys92Arg
Coding: c.275A>G
MANE Select: NM_176822
dbSNP: rs16921697
Type: single nucleotide variant
Location: chr11:7038861 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 92: the pyrin domain; a UniProt-annotated variant site (in); an α-helix

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-lys92arg (accessed [today's date]).

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