Is DNAH5 p.Phe476fs (c.1427_1428del) pathogenic?

DNAH5 p.Phe476fs (c.14271428del) is classified Pathogenic in DNAH5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-12-31). Very rare (popmax 0.000424%, nfe); Associated with DNAH5-related disorders.

What condition is associated with DNAH5 p.Phe476fs (c.1427_1428del)?

DNAH5 p.Phe476fs (c.1427_1428del) is associated with DNAH5-related disorders, primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Phe476fs (c.1427_1428del) in the general population?

DNAH5 p.Phe476fs (c.1427_1428del) is very rare (popmax 0.000424%, nfe) (gnomAD).

DNAH5 p.Phe476fs

c.1427_1428del · rs774493427 · VCV555559

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, 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 11 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.34, phastCons 1
Overall
CADD	33.0	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 0.000424% European (non-Finnish) · 5/1,179,646 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,530 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: DNAH5
Protein: p.Phe476fs
Coding: c.1427_1428del
MANE Select: NM_001369
dbSNP: rs774493427
Type: Deletion
Location: chr5:13913851 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 476: the 'stem' 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 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
DNAH5 p.Ala318fs 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-phe476fs (accessed [today's date]).

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