Is DNAH9 p.Val1997Ala (c.5990T>C) pathogenic?

DNAH9 p.Val1997Ala (c.5990T>C) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-08). AlphaMissense: likely benign (0.3262); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Val1997Ala (c.5990T>C)?

DNAH9 p.Val1997Ala (c.5990T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Val1997Ala (c.5990T>C) in the general population?

DNAH9 p.Val1997Ala (c.5990T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DNAH9 p.Val1997Ala (c.5990T>C)?

AlphaMissense predicts likely benign (score 0.3262) — an in-silico prediction, not a clinical call.

DNAH9 p.Val1997Ala

c.5990T>C · VCV3503755

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3262 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3262	likely benign
REVEL	0.12	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 4.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	25.8	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 0.00167% Admixed American · 1/60,018 alleles

Overall 6.84e-05% 1/1,461,834 alleles · very rare

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.Val1997Ala
Coding: c.5990T>C
MANE Select: NM_001372
Type: single nucleotide variant
Location: chr17:11742192 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 1997: the 'aaa 1' 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.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
DNAH9 p.Ala2657Val 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-val1997ala (accessed [today's date]).

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