Is DNAH5 p.Pro3606fs (c.10815del) pathogenic?

DNAH5 p.Pro3606fs (c.10815del) is classified Pathogenic in DNAH5 (ClinVar, Multiple submitters, 28 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0541%, nfe); Associated with DNAH5-related disorders.

What condition is associated with DNAH5 p.Pro3606fs (c.10815del)?

DNAH5 p.Pro3606fs (c.10815del) is associated with DNAH5-related disorders, primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Pro3606fs (c.10815del) in the general population?

DNAH5 p.Pro3606fs (c.10815del) is ultra-rare (popmax 0.0541%, nfe) (gnomAD).

DNAH5 p.Pro3606fs

c.10815del · rs397515540 · VCV65636

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 28 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0541%, nfe)

Conditions

DNAH5-related disorders

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 63 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0541% European (non-Finnish) · 638/1,179,900 alleles

Filtering AF 0.0506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0492%

Overall 0.0411% 664/1,613,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0541%	1,849
Remaining individualsnot grpmax-eligible	0.032%	3,124
Finnishnot grpmax-eligible	0.00469%	21,341
African / African-American	0.00401%	24,963

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: DNAH5
Protein: p.Pro3606fs
Coding: c.10815del
MANE Select: NM_001369
dbSNP: rs397515540
Type: Deletion
Location: chr5:13753290 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3606: the 'aaa 5' region

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAH5-related disorders

Also linked: primary ciliary dyskinesia 3 primary ciliary dyskinesia

Similar variants

DNAH5 p.Pro3606= Likely benign ★ same residue
DNAH5 c.2577+2del Likely pathogenic ★★ same condition
DNAH5 c.54_57+5del Likely pathogenic ★★ same condition
DNAH5 c.7609+1_7609+3del Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.9605+1del Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Ala1977fs Pathogenic ★★ same condition
DNAH5 p.Ala278fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Ala3121_Leu3122insTer 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/dnah5-p-pro3606fs (accessed [today's date]).

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