Is NLRP14 p.Asp86Val (c.257A>T) pathogenic?

NLRP14 p.Asp86Val (c.257A>T) is classified Benign in NLRP14 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.102); Low-frequency (popmax 1.37%, sas); Associated with spermatogenic failure.

What condition is associated with NLRP14 p.Asp86Val (c.257A>T)?

NLRP14 p.Asp86Val (c.257A>T) is associated with spermatogenic failure (ClinVar).

How common is NLRP14 p.Asp86Val (c.257A>T) in the general population?

NLRP14 p.Asp86Val (c.257A>T) is low-frequency (popmax 1.37%, sas) (gnomAD).

What do computational predictors say about NLRP14 p.Asp86Val (c.257A>T)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

NLRP14 p.Asp86Val

c.257A>T · rs199735773 · VCV979152

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spermatogenic failure

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -8.76	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 1.4	GERP -4, phastCons 0.003
Regional constraint	o/e 1.09	unconstrained · MANE · 33 kb · p 0.0023 · regional, not allelic
Overall
CADD	18.8	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 1.37% South Asian · 1,243/90,876 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0807% 1,302/1,613,524 alleles · low-frequency exomes 1,221/1,461,262 · genomes 81/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.37%	73
Remaining individualsnot grpmax-eligible	0.0736%	1,358
Middle Eastern	0.0496%	2,018
African / African-American	0.00267%	37,511
Admixed American	0.00167%	59,970
European (non-Finnish)	0.000593%	168,556

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.Asp86Val
Coding: c.257A>T
MANE Select: NM_176822
dbSNP: rs199735773
Type: single nucleotide variant
Location: chr11:7038843 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.47 · 4 PDB
Residue 86: the pyrin domain; a UniProt-annotated variant site (increased tendency to form aggregates); an α-helix

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

Disease context

spermatogenic failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NLRP14 p.Lys108Ter Benign ★★ same condition
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-asp86val (accessed [today's date]).

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