Is DNAH9 p.Ala862Ser (c.2584G>T) pathogenic?

DNAH9 p.Ala862Ser (c.2584G>T) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0806); Ultra-rare (popmax 0.0513%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Ala862Ser (c.2584G>T)?

DNAH9 p.Ala862Ser (c.2584G>T) is associated with Inborn genetic diseases, ciliary dyskinesia, primary, 40 (ClinVar).

How common is DNAH9 p.Ala862Ser (c.2584G>T) in the general population?

DNAH9 p.Ala862Ser (c.2584G>T) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

What do computational predictors say about DNAH9 p.Ala862Ser (c.2584G>T)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

DNAH9 p.Ala862Ser

c.2584G>T · rs191974505 · VCV1355800

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.022	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 0.1	GERP -1.6
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	8.795	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 0.0513% East Asian · 23/44,864 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00459% 74/1,613,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0513%	1,951
Remaining individualsnot grpmax-eligible	0.0368%	2,717
South Asian	0.0176%	5,693
Middle Eastern	0.0165%	6,062
African / African-American	0.0147%	6,819

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.Ala862Ser
Coding: c.2584G>T
MANE Select: NM_001372
dbSNP: rs191974505
Type: single nucleotide variant
Location: chr17:11652991 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 862: 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

Also linked: ciliary dyskinesia, primary, 40

Similar variants

DNAH9 p.Ala862Thr Likely benign ★ same residue
DNAH9 c.11406+1G>T Likely pathogenic ★★ same condition
DNAH9 c.1901+1G>A Likely pathogenic ★★ same condition
DNAH9 c.615-2A>G Likely pathogenic ★★ same condition
DNAH9 c.6847+1G>A Likely pathogenic ★★ same condition
DNAH9 p.Arg1344Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Arg1517Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH9 p.Arg1640Ter 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-ala862ser (accessed [today's date]).

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