Is DNAH5 p.Pro363= (c.1089C>T) pathogenic?

DNAH5 p.Pro363= (c.1089C>T) is classified Uncertain significance in DNAH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-19). Very rare (popmax 0.00668%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Pro363= (c.1089C>T)?

DNAH5 p.Pro363= (c.1089C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Pro363= (c.1089C>T) in the general population?

DNAH5 p.Pro363= (c.1089C>T) is very rare (popmax 0.00668%, afr) (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.Pro363=

c.1089C>T · rs763797137 · VCV1932363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

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 -0.23	GERP -3.9, phastCons 0.001
Overall
CADD	2.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,802 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00168% 27/1,608,310 alleles · very rare exomes 22/1,456,178 · genomes 5/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,960
South Asian	0.0033%	30,325
East Asian	0.00223%	44,814
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.00161%	62,304
Finnishnot grpmax-eligible	0.00157%	63,764
European (non-Finnish)	0.00128%	78,340

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.Pro363=
Coding: c.1089C>T
MANE Select: NM_001369
dbSNP: rs763797137
Type: single nucleotide variant
Location: chr5:13917143 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 363: the 'stem' region

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 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
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.1320+1G>A Likely pathogenic ★★ same condition
DNAH5 c.13338+1G>A 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-pro363 (accessed [today's date]).

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