Is DNAH9 p.Pro85Ser (c.253C>T) pathogenic?

DNAH9 p.Pro85Ser (c.253C>T) is classified Uncertain significance in DNAH9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0868); Rare (popmax 0.101%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Pro85Ser (c.253C>T)?

DNAH9 p.Pro85Ser (c.253C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Pro85Ser (c.253C>T) in the general population?

DNAH9 p.Pro85Ser (c.253C>T) is rare (popmax 0.101%, nfe) (gnomAD).

What do computational predictors say about DNAH9 p.Pro85Ser (c.253C>T)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

DNAH9 p.Pro85Ser

c.253C>T · rs762990165 · VCV1367974

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.007	strongly 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 0.8	GERP -3.7
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	3.61	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 0.101% European (non-Finnish) · 1,107/1,096,870 alleles

Filtering AF 0.0959% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0939%

Overall 0.0808% 1,153/1,426,768 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.101%	991
Remaining individualsnot grpmax-eligible	0.0476%	2,101
African / African-American	0.0151%	6,616
Finnishnot grpmax-eligible	0.0142%	7,064
Admixed American	0.0117%	8,543

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.Pro85Ser
Coding: c.253C>T
MANE Select: NM_001372
dbSNP: rs762990165
Type: single nucleotide variant
Location: chr17:11598751 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 85: 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.Pro85= 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
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-pro85ser (accessed [today's date]).

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