Is DNAH5 p.Ile501= (c.1503T>C) pathogenic?

DNAH5 p.Ile501= (c.1503T>C) is classified Benign/Likely benign in DNAH5 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 84.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Ile501= (c.1503T>C)?

DNAH5 p.Ile501= (c.1503T>C) 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.Ile501=

Q: How common is DNAH5 p.Ile501= (c.1503T>C) in the general population?

DNAH5 p.Ile501= (c.1503T>C) is common (popmax 84.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1503T>C · rs3213936 · VCV163158

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 84.2%, eas) — 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.75	GERP -3.7
Overall
CADD	0.834	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 84.2% East Asian · 37,748/44,830 alleles

Filtering AF 83.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 83.2%

Overall 39.6% 638,064/1,612,792 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	84.2%	1
African / African-American	53.2%	2
Middle Eastern	43.4%	2
Ashkenazi Jewishnot grpmax-eligible	42.1%	2
Remaining individualsnot grpmax-eligible	41.1%	2
Admixed American	40%	3
European (non-Finnish)	37.4%	3
South Asian	35.8%	3
Finnishnot grpmax-eligible	33.7%	3
Amishnot grpmax-eligible	31.9%	3

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.Ile501=
Coding: c.1503T>C
MANE Select: NM_001369
dbSNP: rs3213936
Type: single nucleotide variant
Location: chr5:13913776 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 501: the 'stem' region

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)

Similar variants

DNAH5 p.Ile501Thr Uncertain significance ★★ same residue
DNAH5 p.Ile501Val Uncertain significance ★ ⚠ same residue
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

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-ile501 (accessed [today's date]).

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