Is DNAH11 p.Pro99Ser (c.295C>T) pathogenic?

DNAH11 p.Pro99Ser (c.295C>T) is classified Uncertain significance in DNAH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). AlphaMissense: likely benign (0.1132); Very rare (popmax 0.00168%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH11 p.Pro99Ser (c.295C>T)?

DNAH11 p.Pro99Ser (c.295C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH11 p.Pro99Ser (c.295C>T) in the general population?

DNAH11 p.Pro99Ser (c.295C>T) is very rare (popmax 0.00168%, amr) (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.Pro99Ser (c.295C>T)?

AlphaMissense predicts likely benign (score 0.1132) — an in-silico prediction, not a clinical call.

DNAH11 p.Pro99Ser

c.295C>T · VCV4617395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1132	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 358 kb · p 1.1e-96 · regional, not allelic
Overall
CADD	13.73	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

Grpmax group 0.00168% Admixed American · 1/59,474 alleles

Overall 6.21e-05% 1/1,609,364 alleles · very rare exomes 0/1,457,120 · genomes 1/152,244 · joint denominator

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: DNAH11
Protein: p.Pro99Ser
Coding: c.295C>T
MANE Select: NM_001277115
Type: single nucleotide variant
Location: chr7:21543540 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)
Residue 99: the 'stem' region

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)

Similar variants

DNAH11 p.Pro99= Likely benign ★ same residue
DNAH11 p.Pro99Ala Likely benign ★ same residue
DNAH11 c.10166-1G>C Likely pathogenic ★★ same condition
DNAH11 c.10569-2A>G Likely pathogenic ★★ same condition
DNAH11 c.10691+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.10896+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11203-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11839+1G>A 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/dnah11-p-pro99ser (accessed [today's date]).

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