Is DNAI1 p.Val335Phe (c.1003G>T) pathogenic?

DNAI1 p.Val335Phe (c.1003G>T) is classified Conflicting classifications of pathogenicity in DNAI1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-22). AlphaMissense: likely pathogenic (0.9645); Very rare (popmax 0.00133%, afr); Associated with primary ciliary dyskinesia 1.

What condition is associated with DNAI1 p.Val335Phe (c.1003G>T)?

DNAI1 p.Val335Phe (c.1003G>T) is associated with primary ciliary dyskinesia 1, primary ciliary dyskinesia (ClinVar).

How common is DNAI1 p.Val335Phe (c.1003G>T) in the general population?

DNAI1 p.Val335Phe (c.1003G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAI1 p.Val335Phe (c.1003G>T)?

AlphaMissense predicts likely pathogenic (score 0.9645) — an in-silico prediction, not a clinical call.

DNAI1 p.Val335Phe

c.1003G>T · rs11793196 · VCV525451

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9645 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 1

Computational evidence

Protein change
AlphaMissense	0.9645	likely pathogenic · top 5% in DNAI1
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -16.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.35 · regional, not allelic
Overall
CADD	26.9	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 0.00133% African / African-American · 1/74,974 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,678 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,974
European (non-Finnish)	0.000509%	196,643

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: DNAI1
Protein: p.Val335Phe
Coding: c.1003G>T
MANE Select: NM_012144
dbSNP: rs11793196
Type: single nucleotide variant
Location: chr9:34500823 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.54 · 1 PDB
Residue 335: a UniProt-annotated variant site (in)

Full DNAI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAI1 p.Val335Ile Benign/Likely benign ★★ same residue
DNAI1 p.Val335= Likely benign ★ same residue
DNAI1 c.1019+5G>C Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1063+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1063+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAI1 c.1402-1G>A Likely pathogenic ★★ same condition
DNAI1 c.1490-2A>G Likely pathogenic ★★ same condition
DNAI1 c.1569+1G>T Pathogenic/Likely pathogenic ★★ 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/dnai1-p-val335phe (accessed [today's date]).

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