Is DNAH5 p.Arg761fs (c.2283_2284del) pathogenic?

DNAH5 p.Arg761fs (c.22832284del) is classified Pathogenic/Likely pathogenic in DNAH5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-09-15). Very rare (popmax 0.00833%, amr); Associated with DNAH5-related disorders.

What condition is associated with DNAH5 p.Arg761fs (c.2283_2284del)?

DNAH5 p.Arg761fs (c.2283_2284del) is associated with DNAH5-related disorders, primary ciliary dyskinesia 3, primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Arg761fs (c.2283_2284del) in the general population?

DNAH5 p.Arg761fs (c.2283_2284del) is very rare (popmax 0.00833%, amr) (gnomAD).

DNAH5 p.Arg761fs

c.2283_2284del · rs1462578042 · VCV523616

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

DNAH5-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 79
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Overall
CADD	33.0	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 0.00833% Admixed American · 5/59,990 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.0018% 29/1,613,816 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00178%	56,188
African / African-American	0.00133%	74,924

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.Arg761fs
Coding: c.2283_2284del
MANE Select: NM_001369
dbSNP: rs1462578042
Type: Microsatellite
Location: chr5:13894797 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 761: the 'stem' region

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

Disease context

DNAH5-related disorders

Also linked: primary ciliary dyskinesia 3 primary ciliary dyskinesia

Similar variants

DNAH5 p.Arg761Ser Uncertain significance ★★ ⚠ same residue
DNAH5 p.Arg1542fs Pathogenic ★★ same condition
DNAH5 p.Arg2501fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Cys2141_Glu2142delinsTer Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Gln451fs Pathogenic ★★ same condition
DNAH5 p.Glu2633fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Glu3618fs Pathogenic/Likely pathogenic ★★ same condition
DNAH5 p.Glu947fs 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-arg761fs (accessed [today's date]).

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