Is DNAH8 p.Ala184= (c.552G>A) pathogenic?

DNAH8 p.Ala184= (c.552G>A) is classified Likely benign in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). Very rare (popmax 0.00224%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ala184= (c.552G>A)?

DNAH8 p.Ala184= (c.552G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Ala184= (c.552G>A) in the general population?

DNAH8 p.Ala184= (c.552G>A) is very rare (popmax 0.00224%, eas) (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.Ala184=

c.552G>A · rs201672902 · VCV698824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -2.4, phastCons 0.98
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,606 alleles

Filtering AF 0.000363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000263%

Overall 0.00069% 11/1,593,426 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,606
Admixed American	0.0017%	58,816
European (non-Finnish)	0.000771%	129,645

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.Ala184=
Coding: c.552G>A
MANE Select: NM_001206927
dbSNP: rs201672902
Type: single nucleotide variant
Location: chr6:38729928 (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 p.Ala184Val Conflicting classifications of pathogenicity ★ same residue
DNAH8 p.Ala184fs Pathogenic ★ same residue
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

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-ala184 (accessed [today's date]).

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