Is NLRP14 p.Pro271Thr (c.811C>A) pathogenic?

NLRP14 p.Pro271Thr (c.811C>A) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.2565); Ultra-rare (popmax 0.0164%, mid).

How common is NLRP14 p.Pro271Thr (c.811C>A) in the general population?

NLRP14 p.Pro271Thr (c.811C>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about NLRP14 p.Pro271Thr (c.811C>A)?

AlphaMissense predicts likely benign (score 0.2565) — an in-silico prediction, not a clinical call.

NLRP14 p.Pro271Thr

c.811C>A · rs779403071 · VCV2387670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2565	likely benign
REVEL	0.424	indeterminate
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.6	GERP 1.9, phastCons 0.82
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	20.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00757% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00706%

Overall 0.00774% 125/1,614,008 alleles · ultra-rare exomes 118/1,461,874 · genomes 7/152,134 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,701
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00898%	11,132
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00312%	32,017
East Asian	0.00223%	44,892

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro271Thr
Coding: c.811C>A
MANE Select: NM_176822
dbSNP: rs779403071
Type: single nucleotide variant
Location: chr11:7042837 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 271: the nacht domain

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

Similar variants

RBMXL2 p.Gly271Arg 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-pro271thr (accessed [today's date]).

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