Is DNAH9 p.Pro108Ser (c.322C>T) pathogenic?

DNAH9 p.Pro108Ser (c.322C>T) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0855); Very rare (popmax 0.0044%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Pro108Ser (c.322C>T)?

DNAH9 p.Pro108Ser (c.322C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Pro108Ser (c.322C>T) in the general population?

DNAH9 p.Pro108Ser (c.322C>T) is very rare (popmax 0.0044%, amr) (gnomAD).

What do computational predictors say about DNAH9 p.Pro108Ser (c.322C>T)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

DNAH9 p.Pro108Ser

c.322C>T · rs757449453 · VCV1960034

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.063	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 0.18	GERP -3.2
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	5.734	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 0.0044% Admixed American · 2/45,478 alleles

Filtering AF 0.000729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000273%

Overall 0.000335% 5/1,493,632 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0044%	22,739
Remaining individualsnot grpmax-eligible	0.00174%	57,618
African / African-American	0.00145%	69,006
European (non-Finnish)	8.88e-05%	1,125,804

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.Pro108Ser
Coding: c.322C>T
MANE Select: NM_001372
dbSNP: rs757449453
Type: single nucleotide variant
Location: chr17:11598820 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 108: the 'stem' region

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.Pro108Thr Uncertain significance ★ ⚠ same residue
DNAH9 p.Pro108= Likely benign ★ 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

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-pro108ser (accessed [today's date]).

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