Is DNAH5 p.Pro4609= (c.13827T>C) pathogenic?

DNAH5 p.Pro4609= (c.13827T>C) is classified Likely benign in DNAH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-15). Very rare (popmax 0.00167%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Pro4609= (c.13827T>C)?

DNAH5 p.Pro4609= (c.13827T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Pro4609= (c.13827T>C) in the general population?

DNAH5 p.Pro4609= (c.13827T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAH5 p.Pro4609=

c.13827T>C · rs748494424 · VCV1534151

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

primary ciliary dyskinesia

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 -6.3	GERP -5.6
Overall
CADD	0.429	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,004 alleles · very rare exomes 3/1,461,828 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
European (non-Finnish)	0.000254%	393,331

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.Pro4609=
Coding: c.13827T>C
MANE Select: NM_001369
dbSNP: rs748494424
Type: single nucleotide variant
Location: chr5:13692032 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH5 p.Pro4609Ala Uncertain significance ★ same residue
DNAH5 p.Pro4609Ser Uncertain significance same residue
DNAH5 p.Pro4609Thr Uncertain significance ★ same residue
DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A 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-pro4609 (accessed [today's date]).

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