Is DNAH8 p.Pro2322= (c.6966A>T) pathogenic?

DNAH8 p.Pro2322= (c.6966A>T) is classified Benign/Likely benign in DNAH8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.638%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Pro2322= (c.6966A>T)?

DNAH8 p.Pro2322= (c.6966A>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Pro2322= (c.6966A>T) in the general population?

DNAH8 p.Pro2322= (c.6966A>T) is rare (popmax 0.638%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAH8 p.Pro2322=

c.6966A>T · rs149125241 · VCV454588

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.638%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -5.2
Overall
CADD	2.197	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.638% African / African-American · 479/75,028 alleles

Filtering AF 0.591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.573%

Overall 0.0375% 606/1,613,950 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.638%	157
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.056%	1,786
Admixed American	0.0417%	2,401
European (non-Finnish)	0.00509%	19,666
South Asian	0.0022%	45,536

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: DNAH8
Protein: p.Pro2322=
Coding: c.6966A>T
MANE Select: NM_001206927
dbSNP: rs149125241
Type: single nucleotide variant
Location: chr6:38870538 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 2322: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance)

Full DNAH8 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

DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter Pathogenic ★★ same condition
DNAH8 p.Arg4166Ter 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/dnah8-p-pro2322 (accessed [today's date]).

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