Is DNAH7 p.Arg2889Ter (c.8665C>T) pathogenic?

DNAH7 p.Arg2889Ter (c.8665C>T) is classified Likely pathogenic in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Ultra-rare (popmax 0.0164%, mid); Associated with ciliary dyskinesia, primary, 50.

What condition is associated with DNAH7 p.Arg2889Ter (c.8665C>T)?

DNAH7 p.Arg2889Ter (c.8665C>T) is associated with ciliary dyskinesia, primary, 50 (ClinVar).

How common is DNAH7 p.Arg2889Ter (c.8665C>T) in the general population?

DNAH7 p.Arg2889Ter (c.8665C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAH7 p.Arg2889Ter

c.8665C>T · VCV4850652

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

ciliary dyskinesia, primary, 50

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 46 of 65
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.57, phastCons 1
Overall
CADD	38.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000744% 12/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0011%	91,074
European (non-Finnish)	0.000847%	117,999

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: DNAH7
Protein: p.Arg2889Ter
Coding: c.8665C>T
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195853459 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)

Full DNAH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 50 — 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

DNAH7 p.Asn2116Ser Uncertain significance ★★ ⚠ same condition
DNAH7 c.11869-2A>C Likely pathogenic ★ same condition
DNAH7 c.4647+1G>A Pathogenic ★ same condition
DNAH7 c.870-1G>T Likely pathogenic ★ same condition
DNAH7 p.Arg1437Ter Likely pathogenic ★ same condition
DNAH7 p.Gln530Ter Likely pathogenic ★ same condition
DNAH7 p.Met2164Ile Likely pathogenic ★ same condition
DNAH7 p.Trp1759Ter 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/dnah7-p-arg2889ter (accessed [today's date]).

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