Is DNAH11 p.Pro4466Ser (c.13396C>T) pathogenic?

DNAH11 p.Pro4466Ser (c.13396C>T) is classified Uncertain significance in DNAH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-17). AlphaMissense: likely benign (0.1258); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH11 p.Pro4466Ser (c.13396C>T)?

DNAH11 p.Pro4466Ser (c.13396C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH11 p.Pro4466Ser (c.13396C>T) in the general population?

DNAH11 p.Pro4466Ser (c.13396C>T) is absent from gnomAD v4.1 (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 DNAH11 p.Pro4466Ser (c.13396C>T)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

DNAH11 p.Pro4466Ser

c.13396C>T · rs1784797805 · VCV1467325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

primary ciliary dyskinesia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.5	GERP 1.2, phastCons 0.87
Regional constraint	o/e 1.28	unconstrained · MANE · 358 kb · p 1.1e-96 · regional, not allelic
Overall
CADD	16.47	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAH11
Protein: p.Pro4466Ser
Coding: c.13396C>T
MANE Select: NM_001277115
dbSNP: rs1784797805
Type: single nucleotide variant
Location: chr7:21901099 (GRCh38)

Full DNAH11 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)

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/dnah11-p-pro4466ser (accessed [today's date]).

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