Is NXT2 p.Asp64Ter (c.189dup) pathogenic?

NXT2 p.Asp64Ter (c.189dup) is classified Likely pathogenic in NXT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). No allele count reported in gnomAD v4.1 (AN 1,207,532); Associated with male infertility.

What condition is associated with NXT2 p.Asp64Ter (c.189dup)?

NXT2 p.Asp64Ter (c.189dup) is associated with male infertility (ClinVar).

How common is NXT2 p.Asp64Ter (c.189dup) in the general population?

NXT2 p.Asp64Ter (c.189dup) is no allele count reported in gnomAD v4.1 (AN 1,207,532) (gnomAD).

NXT2 p.Asp64Ter

c.189dup · rs2520538578 · VCV3235106

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,207,532)

Conditions

male infertility

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 2, phastCons 0.24

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,207,532). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NXT2
Protein: p.Asp64Ter
Coding: c.189dup
MANE Select: NM_001242617
dbSNP: rs2520538578
Type: Duplication
Location: chrX:109541554 (GRCh38)
Structure: AlphaFold pLDDT 94.35
Residue 64: the ntf2 domain

Full NXT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NXT2 p.Ala35Ser Uncertain significance ★ ⚠ same condition

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/nxt2-p-asp64ter (accessed [today's date]).

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