Is DNAH9 p.Leu2755fs (c.8263del) pathogenic?

DNAH9 p.Leu2755fs (c.8263del) is classified Pathogenic in DNAH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Very rare (popmax 0.000763%, nfe).

How common is DNAH9 p.Leu2755fs (c.8263del) in the general population?

DNAH9 p.Leu2755fs (c.8263del) is very rare (popmax 0.000763%, nfe) (gnomAD).

DNAH9 p.Leu2755fs

c.8263del · VCV4767542

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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 43 of 69
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 0.75, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,004 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 10/1,461,796 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)grpmax	0.000763%	131,112

Remaining individuals 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: DNAH9
Protein: p.Leu2755fs
Coding: c.8263del
MANE Select: NM_001372
Type: Deletion
Location: chr17:11797635 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 2755: a UniProt-annotated variant site (in cild40); a UniProt-annotated variant site (in cild40; loss of localization to cilium axonema)

Full DNAH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH9 c.3354-1del Likely pathogenic ★★ same type
DNAH9 p.Arg995fs Pathogenic ★★ same type
DNAH9 p.Asn780fs Pathogenic/Likely pathogenic ★★ same type
DNAH9 p.Asp3732fs Pathogenic/Likely pathogenic ★★ same type
DNAH9 p.Glu2765fs Pathogenic/Likely pathogenic ★★ same type
DNAH9 p.Leu578fs Pathogenic/Likely pathogenic ★★ same type
DNAH9 p.Phe103fs Pathogenic/Likely pathogenic ★★ same type
DNAH9 p.Phe254fs Pathogenic/Likely pathogenic ★★ same type

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/dnah9-p-leu2755fs (accessed [today's date]).

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