Is DNAH5 p.Val2001Phe (c.6001G>T) pathogenic?

DNAH5 p.Val2001Phe (c.6001G>T) is classified Uncertain significance in DNAH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). AlphaMissense: likely pathogenic (0.9552); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Val2001Phe (c.6001G>T)?

DNAH5 p.Val2001Phe (c.6001G>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Val2001Phe (c.6001G>T) in the general population?

DNAH5 p.Val2001Phe (c.6001G>T) is absent from gnomAD v4.1 (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 DNAH5 p.Val2001Phe (c.6001G>T)?

AlphaMissense predicts likely pathogenic (score 0.9552) — an in-silico prediction, not a clinical call.

DNAH5 p.Val2001Phe

c.6001G>T · rs769656114 · VCV2837614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9552 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.9552	likely pathogenic · top 9% in DNAH5
REVEL	0.705	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAH5
Protein: p.Val2001Phe
Coding: c.6001G>T
MANE Select: NM_001369
dbSNP: rs769656114
Type: single nucleotide variant
Location: chr5:13830657 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2001: the 'aaa 1' region

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH5 p.Val2001Ile Conflicting classifications of pathogenicity ★ same residue
DNAH5 p.Val2001= Likely benign ★ same residue
DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C 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/dnah5-p-val2001phe (accessed [today's date]).

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