Is DNAH9 p.Pro719Ser (c.2155C>T) pathogenic?

DNAH9 p.Pro719Ser (c.2155C>T) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.3403); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Pro719Ser (c.2155C>T)?

DNAH9 p.Pro719Ser (c.2155C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Pro719Ser (c.2155C>T) in the general population?

DNAH9 p.Pro719Ser (c.2155C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DNAH9 p.Pro719Ser (c.2155C>T)?

AlphaMissense predicts ambiguous (score 0.3403) — an in-silico prediction, not a clinical call.

DNAH9 p.Pro719Ser

c.2155C>T · rs140152298 · VCV2181274

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3403	ambiguous
REVEL	0.591	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00217% 35/1,613,806 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
European (non-Finnish)	0.00254%	39,329
Remaining individualsnot grpmax-eligible	0.0016%	62,478
Finnishnot grpmax-eligible	0.00156%	64,018

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.Pro719Ser
Coding: c.2155C>T
MANE Select: NM_001372
dbSNP: rs140152298
Type: single nucleotide variant
Location: chr17:11651126 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 719: 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.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-pro719ser (accessed [today's date]).

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