Is NLRP14 p.Asp735Val (c.2204A>T) pathogenic?

NLRP14 p.Asp735Val (c.2204A>T) is classified Uncertain significance in NLRP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: ambiguous (0.488); Very rare (popmax 8.5e-05%, nfe).

How common is NLRP14 p.Asp735Val (c.2204A>T) in the general population?

NLRP14 p.Asp735Val (c.2204A>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about NLRP14 p.Asp735Val (c.2204A>T)?

AlphaMissense predicts ambiguous (score 0.488) — an in-silico prediction, not a clinical call.

NLRP14 p.Asp735Val

c.2204A>T · VCV3406137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.488	ambiguous
REVEL	0.527	indeterminate
SaProt	LLR -12.19	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	25.1	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 8.5e-05% European (non-Finnish) · 1/1,176,020 alleles

Overall 6.21e-05% 1/1,609,622 alleles · very rare exomes 0/1,457,428 · genomes 1/152,194 · joint denominator

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.Asp735Val
Coding: c.2204A>T
MANE Select: NM_176822
Type: single nucleotide variant
Location: chr11:7049751 (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-asp735val (accessed [today's date]).

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