Is DNAH9 p.Ser3357Phe (c.10070C>T) pathogenic?

DNAH9 p.Ser3357Phe (c.10070C>T) is classified Benign/Likely benign in DNAH9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.6373); Rare (popmax 0.318%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Ser3357Phe (c.10070C>T)?

DNAH9 p.Ser3357Phe (c.10070C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Ser3357Phe (c.10070C>T) in the general population?

DNAH9 p.Ser3357Phe (c.10070C>T) is rare (popmax 0.318%, nfe) (gnomAD).

What do computational predictors say about DNAH9 p.Ser3357Phe (c.10070C>T)?

AlphaMissense predicts likely pathogenic (score 0.6373) — an in-silico prediction, not a clinical call.

DNAH9 p.Ser3357Phe

c.10070C>T · rs146871107 · VCV1165194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6373 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.318%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6373	likely pathogenic
REVEL	0.553	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 333 kb · p 0.00016 · regional, not allelic
Overall
CADD	27.8	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 0.318% European (non-Finnish) · 3,749/1,179,742 alleles

Filtering AF 0.309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.306%

Overall 0.262% 4,225/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
Ashkenazi Jewishnot grpmax-eligible	0.568%	176
European (non-Finnish)grpmax	0.318%	315
Finnishnot grpmax-eligible	0.186%	538
Remaining individualsnot grpmax-eligible	0.186%	539
Admixed American	0.0533%	1,876
African / African-American	0.0373%	2,681
Middle Eastern	0.033%	3,031
South Asian	0.00549%	18,216

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser3357Phe
Coding: c.10070C>T
MANE Select: NM_001372
dbSNP: rs146871107
Type: single nucleotide variant
Location: chr17:11871614 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 3357: 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

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-ser3357phe (accessed [today's date]).

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