Is DNAH5 p.Pro2535= (c.7605C>T) pathogenic?

DNAH5 p.Pro2535= (c.7605C>T) is classified Likely benign in DNAH5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0342%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Pro2535= (c.7605C>T)?

DNAH5 p.Pro2535= (c.7605C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Pro2535= (c.7605C>T) in the general population?

DNAH5 p.Pro2535= (c.7605C>T) is ultra-rare (popmax 0.0342%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAH5 p.Pro2535=

c.7605C>T · rs375573515 · VCV1140866

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, afr)

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 -20	GERP -4.8
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0342% African / African-American · 25/73,142 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0202%

Overall 0.0018% 28/1,551,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0342%	2,926
Remaining individualsnot grpmax-eligible	0.00333%	29,987
Admixed American	0.00194%	51,484

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.Pro2535=
Coding: c.7605C>T
MANE Select: NM_001369
dbSNP: rs375573515
Type: single nucleotide variant
Location: chr5:13810063 (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

primary ciliary dyskinesia — 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)

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-pro2535 (accessed [today's date]).

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