Is DNAH9 p.Ile3417Ser (c.10250T>G) pathogenic?

DNAH9 p.Ile3417Ser (c.10250T>G) is classified Benign/Likely benign in DNAH9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.8301); Low-frequency (popmax 1.16%, afr).

How common is DNAH9 p.Ile3417Ser (c.10250T>G) in the general population?

DNAH9 p.Ile3417Ser (c.10250T>G) is low-frequency (popmax 1.16%, afr) (gnomAD).

What do computational predictors say about DNAH9 p.Ile3417Ser (c.10250T>G)?

AlphaMissense predicts likely pathogenic (score 0.8301) — an in-silico prediction, not a clinical call.

DNAH9 p.Ile3417Ser

c.10250T>G · rs141082617 · VCV1558804

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8301 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.16%, afr)

Computational evidence

Protein change
AlphaMissense	0.8301	likely pathogenic
REVEL	0.39	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	23.6	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 1.16% African / African-American · 869/75,018 alleles

Filtering AF 1.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.0638% 1,029/1,613,416 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.16%	86
Admixed American	0.1%	1,000
Middle Eastern	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0688%	1,453
European (non-Finnish)	0.00432%	23,127

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.Ile3417Ser
Coding: c.10250T>G
MANE Select: NM_001372
dbSNP: rs141082617
Type: single nucleotide variant
Location: chr17:11874956 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 3417: a UniProt-annotated variant site (in cild40); a UniProt-annotated variant site (in cild40; loss of localization to cilium axonema)

Full DNAH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH9 p.Ile3417Met Uncertain significance ★ ⚠ same residue
DNAH9 c.11406+1G>T Likely pathogenic ★★ same type
DNAH9 c.1901+1G>A Likely pathogenic ★★ same type
DNAH9 c.2928+1G>A Likely pathogenic ★★ same type
DNAH9 c.5709+1G>T Likely pathogenic ★★ same type
DNAH9 c.615-2A>G Likely pathogenic ★★ same type
DNAH9 c.6847+1G>A Likely pathogenic ★★ same type
DNAH9 p.Arg1344Ter Pathogenic/Likely pathogenic ★★ same type

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-ile3417ser (accessed [today's date]).

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