Is DNHD1 p.Ala3219fs (c.9655del) pathogenic?

DNHD1 p.Ala3219fs (c.9655del) is classified Likely pathogenic in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). Associated with spermatogenic failure 65.

What condition is associated with DNHD1 p.Ala3219fs (c.9655del)?

DNHD1 p.Ala3219fs (c.9655del) is associated with spermatogenic failure 65 (ClinVar).

DNHD1 p.Ala3219fs

c.9655del · VCV4081344

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 29 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP 0.52, phastCons 1

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

Variant & gene context

Gene: DNHD1
Protein: p.Ala3219fs
Coding: c.9655del
MANE Select: NM_144666
Type: Deletion
Location: chr11:6563116 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3219: 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.Glu4334fs Likely pathogenic ★ same condition
DNHD1 p.Leu1093fs 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-ala3219fs (accessed [today's date]).

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