Is DNAH9 p.Gln445Arg (c.1334A>G) pathogenic?

DNAH9 p.Gln445Arg (c.1334A>G) is classified Benign in DNAH9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0517); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ciliary dyskinesia, primary, 40.

What condition is associated with DNAH9 p.Gln445Arg (c.1334A>G)?

DNAH9 p.Gln445Arg (c.1334A>G) is associated with ciliary dyskinesia, primary, 40 (ClinVar).

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 DNAH9 p.Gln445Arg (c.1334A>G)?

AlphaMissense predicts likely benign (score 0.0517) — an in-silico prediction, not a clinical call.

DNAH9 p.Gln445Arg

Q: How common is DNAH9 p.Gln445Arg (c.1334A>G) in the general population?

DNAH9 p.Gln445Arg (c.1334A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1334A>G · rs9892256 · VCV1233984

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0517 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

ciliary dyskinesia, primary, 40

Computational evidence

Protein change
AlphaMissense	0.0517	likely benign
REVEL	0.162	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -1.2, phastCons 0.98
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	8.648	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 100% East Asian · 44,849/44,850 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.9% 1,608,336/1,610,650 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	100%	1
Ashkenazi Jewishnot grpmax-eligible	100%	1
Amishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
European (non-Finnish)	100%	1
South Asian	100%	1
Remaining individualsnot grpmax-eligible	99.8%	1
Middle Eastern	99.8%	1
Admixed American	99.8%	1
African / African-American	97.3%	1

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAH9
Protein: p.Gln445Arg
Coding: c.1334A>G
MANE Select: NM_001372
dbSNP: rs9892256
Type: single nucleotide variant
Location: chr17:11619765 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 445: the 'stem' region; a UniProt-annotated variant site (in)

Full DNAH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 40 — 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

DNAH9 c.11406+1G>T Likely pathogenic ★★ same condition
DNAH9 c.1901+1G>A Likely pathogenic ★★ same condition
DNAH9 c.615-2A>G Likely pathogenic ★★ same condition
DNAH9 c.6847+1G>A Likely pathogenic ★★ same condition
DNAH9 p.Arg1344Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Arg1517Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Arg1640Ter Likely pathogenic ★★ same condition
DNAH9 p.Arg24Ter 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/dnah9-p-gln445arg (accessed [today's date]).

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