Is DNAH5 p.Asn709Ser (c.2126A>G) pathogenic?

DNAH5 p.Asn709Ser (c.2126A>G) is classified Uncertain significance in DNAH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: ambiguous (0.3623); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 3.

What condition is associated with DNAH5 p.Asn709Ser (c.2126A>G)?

DNAH5 p.Asn709Ser (c.2126A>G) is associated with primary ciliary dyskinesia 3 (ClinVar).

How common is DNAH5 p.Asn709Ser (c.2126A>G) in the general population?

DNAH5 p.Asn709Ser (c.2126A>G) is absent from gnomAD v4.1 (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.Asn709Ser (c.2126A>G)?

AlphaMissense predicts ambiguous (score 0.3623) — an in-silico prediction, not a clinical call.

DNAH5 p.Asn709Ser

c.2126A>G · rs1774434030 · VCV903682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3623 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia 3

Computational evidence

Protein change
AlphaMissense	0.3623	ambiguous
REVEL	0.742	pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAH5
Protein: p.Asn709Ser
Coding: c.2126A>G
dbSNP: rs1774434030
Type: single nucleotide variant
Location: chr5:13900339 (GRCh38)

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 3 — 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/dnah5-p-asn709ser (accessed [today's date]).

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