Is DNAH5 p.Arg2799Trp (c.8395C>T) pathogenic?

DNAH5 p.Arg2799Trp (c.8395C>T) is classified Conflicting classifications of pathogenicity in DNAH5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-15). AlphaMissense: likely pathogenic (0.6346); Ultra-rare (popmax 0.078%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Arg2799Trp (c.8395C>T)?

DNAH5 p.Arg2799Trp (c.8395C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Arg2799Trp (c.8395C>T) in the general population?

DNAH5 p.Arg2799Trp (c.8395C>T) is ultra-rare (popmax 0.078%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about DNAH5 p.Arg2799Trp (c.8395C>T)?

AlphaMissense predicts likely pathogenic (score 0.6346) — an in-silico prediction, not a clinical call.

DNAH5 p.Arg2799Trp

c.8395C>T · rs542159073 · VCV1763199

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6346 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, sas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.6346	likely pathogenic
REVEL	0.605	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.59, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% South Asian · 71/91,070 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00589% 95/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.078%	1,283
Remaining individualsnot grpmax-eligible	0.0176%	5,681
African / African-American	0.004%	25,013
European (non-Finnish)	0.000847%	117,997

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.Arg2799Trp
Coding: c.8395C>T
MANE Select: NM_001369
dbSNP: rs542159073
Type: single nucleotide variant
Location: chr5:13792047 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2799: the 'aaa 3' 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 p.Arg2799Pro Likely pathogenic ★ same residue
DNAH5 p.Arg2799Gln Conflicting classifications of pathogenicity ★ same residue
DNAH5 p.Arg2799= Likely benign ★ 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-arg2799trp (accessed [today's date]).

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