Is DNAH8 p.Arg3123= (c.9369A>G) pathogenic?

DNAH8 p.Arg3123= (c.9369A>G) is classified Benign in DNAH8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Arg3123= (c.9369A>G)?

DNAH8 p.Arg3123= (c.9369A>G) is associated with primary ciliary dyskinesia (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DNAH8 p.Arg3123=

Q: How common is DNAH8 p.Arg3123= (c.9369A>G) in the general population?

DNAH8 p.Arg3123= (c.9369A>G) is common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9369A>G · rs4452640 · VCV1168411

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 27.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.81	GERP -5.2
Overall
CADD	3.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.5% East Asian · 12,210/44,400 alleles

Filtering AF 27.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.9%

Overall 4.02% 64,588/1,606,560 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	27.5%	4
African / African-American	10.3%	10
Admixed American	8.23%	12
Finnishnot grpmax-eligible	5.76%	17
Amishnot grpmax-eligible	5.59%	18
South Asian	5.02%	20
Remaining individualsnot grpmax-eligible	4.79%	21
Middle Eastern	2.64%	38
European (non-Finnish)	2.37%	42
Ashkenazi Jewishnot grpmax-eligible	2.02%	49

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.Arg3123=
Coding: c.9369A>G
dbSNP: rs4452640
Type: single nucleotide variant
Location: chr6:38907976 (GRCh38)

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)

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-arg3123 (accessed [today's date]).

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