Is NLRP14 p.Ala301Pro (c.901G>C) pathogenic?

NLRP14 p.Ala301Pro (c.901G>C) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely pathogenic (0.8257); Very rare (popmax 0.00549%, sas).

How common is NLRP14 p.Ala301Pro (c.901G>C) in the general population?

NLRP14 p.Ala301Pro (c.901G>C) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about NLRP14 p.Ala301Pro (c.901G>C)?

AlphaMissense predicts likely pathogenic (score 0.8257) — an in-silico prediction, not a clinical call.

NLRP14 p.Ala301Pro

c.901G>C · rs765889075 · VCV2606174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8257 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8257	likely pathogenic · top 3% in NLRP14
REVEL	0.628	indeterminate
SaProt	LLR -14.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -2.1, phastCons 0.49
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	17.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00549% South Asian · 5/91,076 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000558% 9/1,614,028 alleles · very rare exomes 9/1,461,746 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00017%	589,950

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.Ala301Pro
Coding: c.901G>C
MANE Select: NM_176822
dbSNP: rs765889075
Type: single nucleotide variant
Location: chr11:7042927 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 301: the nacht domain

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-ala301pro (accessed [today's date]).

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