Is DNAH5 p.Trp3503Ter (c.10508G>A) pathogenic?

DNAH5 p.Trp3503Ter (c.10508G>A) is classified Pathogenic in DNAH5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). Very rare (popmax 0.0022%, sas); Associated with Respiratory ciliopathies including non-CF bronchiectasis.

How common is DNAH5 p.Trp3503Ter (c.10508G>A) in the general population?

DNAH5 p.Trp3503Ter (c.10508G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

DNAH5 p.Trp3503Ter

Q: What condition is associated with DNAH5 p.Trp3503Ter (c.10508G>A)?

DNAH5 p.Trp3503Ter (c.10508G>A) is associated with Respiratory ciliopathies including non-CF bronchiectasis, primary ciliary dyskinesia (ClinVar).

c.10508G>A · rs777987305 · VCV1458959

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Respiratory ciliopathies including non-CF bronchiectasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 62 of 79
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,820 alleles · very rare

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.Trp3503Ter
Coding: c.10508G>A
MANE Select: NM_001369
dbSNP: rs777987305
Type: single nucleotide variant
Location: chr5:13754250 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

Respiratory ciliopathies including non-CF bronchiectasis

Also linked: primary ciliary dyskinesia

Similar variants

DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.1320+1G>A Likely pathogenic ★★ same condition
DNAH5 c.13338+1G>A 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/dnah5-p-trp3503ter (accessed [today's date]).

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