Is TRPV4 p.His299fs (c.895dup) pathogenic?

TRPV4 p.His299fs (c.895dup) is classified Uncertain significance in TRPV4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-28). No gnomAD frequency available for this variant; Associated with Charcot-Marie-Tooth disease axonal type 2C.

What condition is associated with TRPV4 p.His299fs (c.895dup)?

TRPV4 p.His299fs (c.895dup) is associated with Charcot-Marie-Tooth disease axonal type 2C (ClinVar).

How common is TRPV4 p.His299fs (c.895dup) in the general population?

TRPV4 p.His299fs (c.895dup) is no gnomAD frequency available for this variant (gnomAD).

TRPV4 p.His299fs

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2C inherited?

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

c.895dup · rs2548750687 · VCV2163625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Charcot-Marie-Tooth disease axonal type 2C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP -0.57, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRPV4
Protein: p.His299fs
Coding: c.895dup
MANE Select: NM_021625
dbSNP: rs2548750687
Type: Duplication
Location: chr12:109798870 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 19 PDB
Residue 299: an α-helix; a binding site

Full TRPV4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease axonal type 2C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant Charcot-Marie-Tooth disease type 2C (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

TRPV4 p.His299= Likely benign ★ same residue
TRPV4 c.713-2dup Uncertain significance ★★ same condition
TRPV4 c.1152+19dup Benign/Likely benign ★★ same condition
TRPV4 c.1584+17dup Benign/Likely benign ★★ same condition
TRPV4 c.2209-13_2209-5dup Uncertain significance ★ same condition
TRPV4 p.Arg510fs Uncertain significance ★ same condition
TRPV4 p.Glu29fs Uncertain significance ★ same condition
TRPV4 p.Lys192fs 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/trpv4-p-his299fs (accessed [today's date]).

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