Is DNAH9 p.Ser351Pro (c.1051T>C) pathogenic?

DNAH9 p.Ser351Pro (c.1051T>C) is classified Uncertain significance in DNAH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-28). AlphaMissense: likely benign (0.1698); Very rare (popmax 0.00153%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH9 p.Ser351Pro (c.1051T>C)?

DNAH9 p.Ser351Pro (c.1051T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH9 p.Ser351Pro (c.1051T>C) in the general population?

DNAH9 p.Ser351Pro (c.1051T>C) is very rare (popmax 0.00153%, 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.Ser351Pro (c.1051T>C)?

AlphaMissense predicts likely benign (score 0.1698) — an in-silico prediction, not a clinical call.

DNAH9 p.Ser351Pro

c.1051T>C · rs770389199 · VCV977572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1698	likely benign
REVEL	0.099	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 0.99	GERP -3.7, phastCons 0.013
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	16.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,180,020 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,614,012 alleles · very rare

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.Ser351Pro
Coding: c.1051T>C
MANE Select: NM_001372
dbSNP: rs770389199
Type: single nucleotide variant
Location: chr17:11617557 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 351: the 'stem' region

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.Arg2395Trp Uncertain significance ★★ same condition
DNAH9 p.Gln2390Pro Uncertain significance ★★ same condition
DNAH9 p.Gln4455Arg Uncertain significance ★★ ⚠ same condition
DNAH9 p.Pro1868Ser Uncertain significance ★★ same condition
DNAH9 p.Thr3375Arg Uncertain significance ★★ same condition
DNAH9 p.Leu1176Pro Uncertain significance ★ ⚠ same condition
DNAH9 p.Phe103fs Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Pro2957fs 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-ser351pro (accessed [today's date]).

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