Is DNHD1 p.Leu1093fs (c.3278del) pathogenic?

DNHD1 p.Leu1093fs (c.3278del) is classified Likely pathogenic in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Ultra-rare (popmax 0.0168%, mid); Associated with spermatogenic failure 65.

What condition is associated with DNHD1 p.Leu1093fs (c.3278del)?

DNHD1 p.Leu1093fs (c.3278del) is associated with spermatogenic failure 65 (ClinVar).

How common is DNHD1 p.Leu1093fs (c.3278del) in the general population?

DNHD1 p.Leu1093fs (c.3278del) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

DNHD1 p.Leu1093fs

c.3278del · VCV4277579

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Conditions

spermatogenic failure 65

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP 0.74, phastCons 0.97

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,946 alleles

Overall 7.2e-05% 1/1,388,508 alleles · ultra-rare

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: DNHD1
Protein: p.Leu1093fs
Coding: c.3278del
MANE Select: NM_144666
Type: Deletion
Location: chr11:6538763 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

Full DNHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 65 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNHD1 p.Ala3219fs Likely pathogenic ★ same condition
DNHD1 p.Glu4334fs Likely pathogenic ★ same condition
DNHD1 p.Thr970fs Likely pathogenic ★ same condition
DNHD1 p.Tyr676fs Likely pathogenic ★ same condition
DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same condition
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same condition
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same condition
DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ 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/dnhd1-p-leu1093fs (accessed [today's date]).

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