Is DNAH5 p.Arg1458= (c.4374G>T) pathogenic?

DNAH5 p.Arg1458= (c.4374G>T) is classified Benign in DNAH5 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 46.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Arg1458= (c.4374G>T)?

DNAH5 p.Arg1458= (c.4374G>T) 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.Arg1458=

Q: How common is DNAH5 p.Arg1458= (c.4374G>T) in the general population?

DNAH5 p.Arg1458= (c.4374G>T) is common (popmax 46.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4374G>T · rs6554827 · VCV178750

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 46.8%, sas) — 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 -1.3	GERP -3.4
Overall
CADD	5.097	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 46.8% South Asian · 42,633/91,054 alleles

Filtering AF 46.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.3%

Overall 42.9% 692,671/1,613,476 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	47.9%	2
South Asiangrpmax	46.8%	2
European (non-Finnish)	44.6%	2
Remaining individualsnot grpmax-eligible	41.6%	2
Ashkenazi Jewishnot grpmax-eligible	35.8%	3
Middle Eastern	34.9%	3
Amishnot grpmax-eligible	32.3%	3
African / African-American	31.8%	3
Admixed American	31.2%	3
East Asian	25.9%	4

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1458=
Coding: c.4374G>T
MANE Select: NM_001369
dbSNP: rs6554827
Type: single nucleotide variant
Location: chr5:13864619 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1458: 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.Arg1458Gln Benign/Likely benign ★★ same residue
DNAH5 p.Arg1458Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DNAH5 p.Arg1458His 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

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-arg1458 (accessed [today's date]).

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