Is DNAH9 p.Pro1868Ser (c.5602C>T) pathogenic?

DNAH9 p.Pro1868Ser (c.5602C>T) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.913); Very rare (popmax 0.00178%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH9 p.Pro1868Ser (c.5602C>T)?

DNAH9 p.Pro1868Ser (c.5602C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH9 p.Pro1868Ser (c.5602C>T) in the general population?

DNAH9 p.Pro1868Ser (c.5602C>T) is very rare (popmax 0.00178%, nfe) (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 DNAH9 p.Pro1868Ser (c.5602C>T)?

AlphaMissense predicts likely pathogenic (score 0.913) — an in-silico prediction, not a clinical call.

DNAH9 p.Pro1868Ser

c.5602C>T · rs145930162 · VCV1496206

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.913	likely pathogenic · top 8% in DNAH9
REVEL	0.44	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	28.2	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 0.00178% European (non-Finnish) · 21/1,180,008 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,613,986 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,003
European (non-Finnish)grpmax	0.00178%	56,191
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro1868Ser
Coding: c.5602C>T
MANE Select: NM_001372
dbSNP: rs145930162
Type: single nucleotide variant
Location: chr17:11719383 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 1868: the 'aaa 1' region; a UniProt-annotated variant site (in cild40)

Full DNAH9 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

DNAH9 p.Pro1868= Benign ★★ same residue
DNAH9 p.Arg2395Trp Uncertain significance ★★ same condition
DNAH9 p.Gln2390Pro Uncertain significance ★★ same condition
DNAH9 p.Gln4455Arg Uncertain significance ★★ ⚠ same condition
DNAH9 p.Thr3375Arg Uncertain significance ★★ same condition
DNAH9 p.Leu1176Pro Uncertain significance ★ ⚠ same condition
DNAH9 p.Ser351Pro Uncertain significance ★ ⚠ same condition
DNAH9 p.Phe103fs 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-pro1868ser (accessed [today's date]).

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