Is DNAH9 p.Ile4002Val (c.12004A>G) pathogenic?

DNAH9 p.Ile4002Val (c.12004A>G) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0649); Rare (popmax 0.118%, amr); Associated with DNAH9-related disorder.

What condition is associated with DNAH9 p.Ile4002Val (c.12004A>G)?

DNAH9 p.Ile4002Val (c.12004A>G) is associated with DNAH9-related disorder (ClinVar).

How common is DNAH9 p.Ile4002Val (c.12004A>G) in the general population?

DNAH9 p.Ile4002Val (c.12004A>G) is rare (popmax 0.118%, amr) (gnomAD).

What do computational predictors say about DNAH9 p.Ile4002Val (c.12004A>G)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

DNAH9 p.Ile4002Val

c.12004A>G · rs200659309 · VCV1390539

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.118%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

DNAH9-related disorder

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.027	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -2.3, phastCons 0.003
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	13.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% Admixed American · 71/60,010 alleles

Filtering AF 0.0962% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.088%

Overall 0.00533% 86/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.118%	845
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.000932%	107,273

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.Ile4002Val
Coding: c.12004A>G
MANE Select: NM_001372
dbSNP: rs200659309
Type: single nucleotide variant
Location: chr17:11929992 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 4002: a UniProt-annotated variant site (in cild40); a UniProt-annotated variant site (in cild40; loss of localization to cilium axonema); the 'aaa 6' region

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

Disease context

DNAH9-related disorder

Similar variants

DNAH9 c.2928+1G>A Likely pathogenic ★★ same condition
DNAH9 c.5709+1G>T Likely pathogenic ★★ same condition
DNAH9 p.Arg1640Ter Likely pathogenic ★★ same condition
DNAH9 p.Arg3779Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Arg4065Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Gln1266Ter Pathogenic ★★ same condition
DNAH9 p.Gln3469Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Trp346Ter 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/dnah9-p-ile4002val (accessed [today's date]).

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