Is DNAH5 p.Arg827= (c.2481C>T) pathogenic?

DNAH5 p.Arg827= (c.2481C>T) is classified Conflicting classifications of pathogenicity in DNAH5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-02). Rare (popmax 0.195%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Arg827= (c.2481C>T)?

DNAH5 p.Arg827= (c.2481C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Arg827= (c.2481C>T) in the general population?

DNAH5 p.Arg827= (c.2481C>T) is rare (popmax 0.195%, sas) (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.Arg827=

c.2481C>T · rs777353326 · VCV525547

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.195%, sas)

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 0.44	GERP 1, phastCons 0.99
Overall
CADD	5.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.195% South Asian · 178/91,080 alleles

Filtering AF 0.172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.0122% 197/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.195%	512
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.000763%	131,110

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.Arg827=
Coding: c.2481C>T
MANE Select: NM_001369
dbSNP: rs777353326
Type: single nucleotide variant
Location: chr5:13891072 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 827: 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

Also linked: primary ciliary dyskinesia 3

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.Arg827Cys Uncertain significance ★★ same residue
DNAH5 p.Arg827Ser 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
DNAH5 c.12910-1G>C 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-arg827 (accessed [today's date]).

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