Is NLRP14 p.Ser1069Arg (c.3207C>G) pathogenic?

NLRP14 p.Ser1069Arg (c.3207C>G) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1987); Ultra-rare (popmax 0.0718%, amr).

How common is NLRP14 p.Ser1069Arg (c.3207C>G) in the general population?

NLRP14 p.Ser1069Arg (c.3207C>G) is ultra-rare (popmax 0.0718%, amr) (gnomAD).

What do computational predictors say about NLRP14 p.Ser1069Arg (c.3207C>G)?

AlphaMissense predicts likely benign (score 0.1987) — an in-silico prediction, not a clinical call.

NLRP14 p.Ser1069Arg

c.3207C>G · VCV4120617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0718%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1987	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.62	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 -0.16	GERP -0.15, phastCons 0.37
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	13.06	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0718% Admixed American · 43/59,884 alleles

Filtering AF 0.0547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0487%

Overall 0.00279% 45/1,612,578 alleles · ultra-rare exomes 41/1,461,178 · genomes 4/151,400 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0718%	1,393
Remaining individualsnot grpmax-eligible	0.0032%	31,223

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.Ser1069Arg
Coding: c.3207C>G
MANE Select: NM_176822
Type: single nucleotide variant
Location: chr11:7071233 (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

NLRP14 p.Ser1069Cys 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
NLRP14 c.-21-48T>A 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-ser1069arg (accessed [today's date]).

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