Is DNAH5 p.Arg1245His (c.3734G>A) pathogenic?

DNAH5 p.Arg1245His (c.3734G>A) is classified Conflicting classifications of pathogenicity in DNAH5 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-05). AlphaMissense: likely benign (0.0911); Rare (popmax 0.687%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Arg1245His (c.3734G>A)?

DNAH5 p.Arg1245His (c.3734G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Arg1245His (c.3734G>A) in the general population?

DNAH5 p.Arg1245His (c.3734G>A) is rare (popmax 0.687%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about DNAH5 p.Arg1245His (c.3734G>A)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

DNAH5 p.Arg1245His

c.3734G>A · rs77939839 · VCV195808

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.687%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.287	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.687% African / African-American · 515/75,008 alleles

Filtering AF 0.638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.618%

Overall 0.046% 743/1,613,776 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.687%	146
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Admixed American	0.0534%	1,873
Middle Eastern	0.033%	3,030
South Asian	0.0198%	5,060
European (non-Finnish)	0.0111%	9,006
East Asian	0.00669%	14,957

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.Arg1245His
Coding: c.3734G>A
dbSNP: rs77939839
Type: single nucleotide variant
Location: chr5:13870867 (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-arg1245his (accessed [today's date]).

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