Is NLRP14 p.Arg657His (c.1970G>A) pathogenic?

NLRP14 p.Arg657His (c.1970G>A) is classified Likely benign in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0675); Very rare (popmax 0.00271%, nfe).

How common is NLRP14 p.Arg657His (c.1970G>A) in the general population?

NLRP14 p.Arg657His (c.1970G>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about NLRP14 p.Arg657His (c.1970G>A)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

NLRP14 p.Arg657His

c.1970G>A · VCV3920253

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -4.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.5	GERP -3.3
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	0.007	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 0.00271% European (non-Finnish) · 32/1,179,136 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,612,982 alleles · very rare exomes 32/1,460,872 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,848
Remaining individualsnot grpmax-eligible	0.0016%	62,444
African / African-American	0.00134%	74,854

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.Arg657His
Coding: c.1970G>A
MANE Select: NM_176822
Type: single nucleotide variant
Location: chr11:7046679 (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-arg657his (accessed [today's date]).

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