Is DNAH11 p.Ala4022Pro (c.12064G>C) pathogenic?

DNAH11 p.Ala4022Pro (c.12064G>C) is classified Likely pathogenic in DNAH11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-06). AlphaMissense: likely pathogenic (0.88); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 7.

What condition is associated with DNAH11 p.Ala4022Pro (c.12064G>C)?

DNAH11 p.Ala4022Pro (c.12064G>C) is associated with primary ciliary dyskinesia 7 (ClinVar).

How common is DNAH11 p.Ala4022Pro (c.12064G>C) in the general population?

DNAH11 p.Ala4022Pro (c.12064G>C) 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.Ala4022Pro (c.12064G>C)?

AlphaMissense predicts likely pathogenic (score 0.88) — an in-silico prediction, not a clinical call.

DNAH11 p.Ala4022Pro

c.12064G>C · rs72658819 · VCV1804935

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.88 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia 7

Computational evidence

Protein change
AlphaMissense	0.88	likely pathogenic ✓ concordant with ClinVar · top 5% in DNAH11
REVEL	0.347	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 358 kb · p 1.1e-96 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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.Ala4022Pro
Coding: c.12064G>C
MANE Select: NM_001277115
dbSNP: rs72658819
Type: single nucleotide variant
Location: chr7:21873370 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)
Residue 4022: the 'aaa 6' region

Full DNAH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 7 — 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.Ala4022= Likely benign ★ same residue
DNAH11 c.10166-1G>C Likely pathogenic ★★ same condition
DNAH11 c.10691+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11839+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.11968-1G>C Pathogenic ★★ same condition
DNAH11 c.12934-1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.1710+1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH11 c.3426-1G>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-ala4022pro (accessed [today's date]).

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