Is DNHD1 p.Pro3507fs (c.10517_10518insGGGAGAGGGACACACTC) pathogenic?

DNHD1 p.Pro3507fs (c.1051710518insGGGAGAGGGACACACTC) is classified Likely pathogenic in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). Very rare (popmax 0.000174%, nfe); Associated with spermatogenic failure 65.

What condition is associated with DNHD1 p.Pro3507fs (c.10517_10518insGGGAGAGGGACACACTC)?

DNHD1 p.Pro3507fs (c.10517_10518insGGGAGAGGGACACACTC) is associated with spermatogenic failure 65 (ClinVar).

How common is DNHD1 p.Pro3507fs (c.10517_10518insGGGAGAGGGACACACTC) in the general population?

DNHD1 p.Pro3507fs (c.10517_10518insGGGAGAGGGACACACTC) is very rare (popmax 0.000174%, nfe) (gnomAD).

DNHD1 p.Pro3507fs

c.10517_10518insGGGAGAGGGACACACTC · VCV3779275

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

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 32 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.42	GERP 0.42, phastCons 0.95

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,992 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000143% 2/1,399,414 alleles · very 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.Pro3507fs
Coding: c.10517_10518insGGGAGAGGGACACACTC
MANE Select: NM_144666
Type: Microsatellite
Location: chr11:6564557 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3507: a UniProt-annotated variant site (in spgf65); a UniProt-annotated variant site (in spgf65; low expression, if any, in sperm flagella)

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.Arg174fs Pathogenic ★ same condition
DNHD1 p.Trp3958fs Likely pathogenic ★ same condition
DNHD1 p.Pro3507Ala Uncertain significance ★ ⚠ same residue
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
DNHD1 p.Tyr2166Ter 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-pro3507fs (accessed [today's date]).

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