Is DNAH8 p.Ala350= (c.1050C>T) pathogenic?

DNAH8 p.Ala350= (c.1050C>T) is classified Benign in DNAH8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 10.1%, sas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ala350= (c.1050C>T)?

DNAH8 p.Ala350= (c.1050C>T) 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.Ala350=

Q: How common is DNAH8 p.Ala350= (c.1050C>T) in the general population?

DNAH8 p.Ala350= (c.1050C>T) is common (popmax 10.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1050C>T · rs9470924 · VCV414417

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.1%, sas) — 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -5.9
Overall
CADD	0.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% South Asian · 9,139/90,162 alleles

Filtering AF 9.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.89%

Overall 1.92% 30,792/1,605,436 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	10.1%	10
East Asian	4.43%	23
Middle Eastern	2.65%	38
Amishnot grpmax-eligible	2.63%	38
Remaining individualsnot grpmax-eligible	2.14%	47
Admixed American	1.63%	61
Finnishnot grpmax-eligible	1.62%	62
European (non-Finnish)	1.33%	75
Ashkenazi Jewishnot grpmax-eligible	1.17%	86
African / African-American	0.325%	308

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.Ala350=
Coding: c.1050C>T
MANE Select: NM_001206927
dbSNP: rs9470924
Type: single nucleotide variant
Location: chr6:38737906 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

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-ala350 (accessed [today's date]).

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