Is DNHD1 p.Pro4094= (c.12282G>A) pathogenic?

DNHD1 p.Pro4094= (c.12282G>A) is classified Likely benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-08). Ultra-rare (popmax 0.0998%, nfe); Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Pro4094= (c.12282G>A)?

DNHD1 p.Pro4094= (c.12282G>A) is associated with DNHD1-related disorder (ClinVar).

How common is DNHD1 p.Pro4094= (c.12282G>A) in the general population?

DNHD1 p.Pro4094= (c.12282G>A) is ultra-rare (popmax 0.0998%, nfe) (gnomAD).

DNHD1 p.Pro4094=

c.12282G>A · rs201927512 · VCV3035370

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0998%, nfe)

Conditions

DNHD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -3.6
Overall
CADD	1.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0998% European (non-Finnish) · 1,177/1,179,882 alleles

Filtering AF 0.0949% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0931%

Overall 0.0776% 1,252/1,613,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0998%	1,002
African / African-American	0.0573%	1,745
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Admixed American	0.00833%	12,006
South Asian	0.00659%	15,180
Finnishnot grpmax-eligible	0.00627%	15,941
East Asian	0.00223%	44,888

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.Pro4094=
Coding: c.12282G>A
MANE Select: NM_144666
dbSNP: rs201927512
Type: single nucleotide variant
Location: chr11:6567791 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 4094: 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

DNHD1-related disorder

Similar variants

DNHD1 p.Pro4094Leu Likely benign ★ same residue
DNHD1 p.Glu4486Lys Uncertain significance ★★ ⚠ same condition
DNHD1 p.His4162Leu Uncertain significance ★★ ⚠ same condition
DNHD1 p.Arg2840Gln Uncertain significance ★ ⚠ same condition
DNHD1 p.Gln895Ter Conflicting classifications of pathogenicity ★ same condition
DNHD1 p.His3335Arg Uncertain significance ★ ⚠ same condition
DNHD1 p.Ala657Ser Uncertain significance ⚠ same condition
DNHD1 p.Glu971Lys 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/dnhd1-p-pro4094 (accessed [today's date]).

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