Is DNAH9 p.Ile1509Met (c.4527C>G) pathogenic?

DNAH9 p.Ile1509Met (c.4527C>G) is classified Uncertain significance in DNAH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely benign (0.0895); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Ile1509Met (c.4527C>G)?

DNAH9 p.Ile1509Met (c.4527C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Ile1509Met (c.4527C>G) in the general population?

DNAH9 p.Ile1509Met (c.4527C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAH9 p.Ile1509Met (c.4527C>G)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

DNAH9 p.Ile1509Met

c.4527C>G · rs2544413369 · VCV2623145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.369	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.015, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	16.47	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAH9
Protein: p.Ile1509Met
Coding: c.4527C>G
MANE Select: NM_001372
dbSNP: rs2544413369
Type: single nucleotide variant
Location: chr17:11690349 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 1509: the 'stem' region; a UniProt-annotated variant site (in cild40)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH9 p.Ile1509Val Uncertain significance ★ ⚠ same residue
DNAH9 p.Ala1534Ser Uncertain significance ★★ ⚠ same condition
DNAH9 p.Ala1719Thr Uncertain significance ★★ ⚠ same condition
DNAH9 p.Ala1755Thr Uncertain significance ★★ ⚠ same condition
DNAH9 p.Ala1795Thr Uncertain significance ★★ ⚠ same condition
DNAH9 p.Ala1869Thr Uncertain significance ★★ ⚠ same condition
DNAH9 p.Ala2046Thr Uncertain significance ★★ same condition
DNAH9 p.Ala2100Thr Uncertain significance ★★ ⚠ 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-ile1509met (accessed [today's date]).

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