Is DNAH5 p.Ser1477= (c.4431C>T) pathogenic?

DNAH5 p.Ser1477= (c.4431C>T) is classified Benign in DNAH5 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-03). Common (popmax 7.04%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Ser1477= (c.4431C>T)?

DNAH5 p.Ser1477= (c.4431C>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DNAH5 p.Ser1477=

Q: How common is DNAH5 p.Ser1477= (c.4431C>T) in the general population?

DNAH5 p.Ser1477= (c.4431C>T) is common (popmax 7.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4431C>T · rs74451896 · VCV258034

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 7.04%, afr) — 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
Pangolin	Δ0.37	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -2.3	GERP -3.7
Overall
CADD	18.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.04% African / African-American · 5,277/74,948 alleles

Filtering AF 6.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.82%

Overall 0.376% 6,071/1,613,982 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.04%	14
Admixed American	0.505%	198
Remaining individualsnot grpmax-eligible	0.474%	211
Middle Eastern	0.247%	404
East Asian	0.0201%	4,987
South Asian	0.0143%	7,005
European (non-Finnish)	0.0134%	7,468

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: DNAH5
Protein: p.Ser1477=
Coding: c.4431C>T
dbSNP: rs74451896
Type: single nucleotide variant
Location: chr5:13864562 (GRCh38)

Full DNAH5 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

Also linked: primary ciliary dyskinesia 3

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/dnah5-p-ser1477 (accessed [today's date]).

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