Is DNAH9 p.Phe103Ser (c.308T>C) pathogenic?

DNAH9 p.Phe103Ser (c.308T>C) is classified Conflicting classifications of pathogenicity in DNAH9 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-25). AlphaMissense: likely pathogenic (0.922); Ultra-rare (popmax 0.0956%, eas); Associated with Inborn genetic diseases.

What condition is associated with DNAH9 p.Phe103Ser (c.308T>C)?

DNAH9 p.Phe103Ser (c.308T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH9 p.Phe103Ser (c.308T>C) in the general population?

DNAH9 p.Phe103Ser (c.308T>C) is ultra-rare (popmax 0.0956%, eas) (gnomAD).

What do computational predictors say about DNAH9 p.Phe103Ser (c.308T>C)?

AlphaMissense predicts likely pathogenic (score 0.922) — an in-silico prediction, not a clinical call.

DNAH9 p.Phe103Ser

c.308T>C · rs373784591 · VCV1630804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0956%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.922	likely pathogenic · top 7% in DNAH9
REVEL	0.235	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.43, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 34 kb · p 0.0046 · regional, not allelic
Overall
CADD	18.2	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 0.0956% East Asian · 34/35,574 alleles

Filtering AF 0.0702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0616%

Overall 0.0396% 587/1,480,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0956%	1,046
Middle Eastern	0.0548%	1,826
Remaining individualsnot grpmax-eligible	0.0457%	2,190
European (non-Finnish)	0.0439%	2,276
South Asian	0.025%	3,993
African / African-American	0.0102%	9,765
Finnishnot grpmax-eligible	0.00667%	14,996
Admixed American	0.00468%	21,388

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.Phe103Ser
Coding: c.308T>C
MANE Select: NM_001372
dbSNP: rs373784591
Type: single nucleotide variant
Location: chr17:11598806 (GRCh38)
Gene constraint: LOEUF 0.775 · pLI <0.01 (gnomAD)
Residue 103: 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.Phe103Cys Likely benign ★★ ⚠ same residue
DNAH9 p.Phe103Leu Benign/Likely benign ★★ ⚠ same residue
DNAH9 p.Phe103Tyr Uncertain significance ★ ⚠ same residue
DNAH9 p.Phe103fs Pathogenic/Likely pathogenic ★★ 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

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-phe103ser (accessed [today's date]).

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