Is TRPV4 p.Pro230= (c.690C>T) pathogenic?

TRPV4 p.Pro230= (c.690C>T) is classified Likely benign in TRPV4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-02). Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRPV4 p.Pro230= (c.690C>T)?

TRPV4 p.Pro230= (c.690C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2C (ClinVar).

How common is TRPV4 p.Pro230= (c.690C>T) in the general population?

TRPV4 p.Pro230= (c.690C>T) is very rare (popmax 0.01%, amr) (gnomAD).

TRPV4 p.Pro230=

c.690C>T · rs747822070 · VCV512273

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -4.1, phastCons 1
Overall
CADD	6.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,010 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,613,984 alleles · very rare exomes 6/1,461,736 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: TRPV4
Protein: p.Pro230=
Coding: c.690C>T
MANE Select: NM_021625
dbSNP: rs747822070
Type: single nucleotide variant
Location: chr12:109803013 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 19 PDB
Residue 230: an α-helix

Full TRPV4 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

Also linked: Charcot-Marie-Tooth disease axonal type 2C

Similar variants

TRPV4 p.Pro230Ala Uncertain significance ★ same residue
TRPV4 p.Pro230Leu Uncertain significance ★ ⚠ same residue
TRPV4 p.Pro230Ser Likely pathogenic ⚠ same residue
TRPV4 p.Arg186Gln Pathogenic/Likely pathogenic ★★ same condition
TRPV4 p.Arg232Cys Pathogenic ★★ ⚠ same condition
TRPV4 p.Arg269Cys Pathogenic ★★ ⚠ same condition
TRPV4 p.Arg269His Pathogenic/Likely pathogenic ★★ same condition
TRPV4 p.Arg315Gln 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/trpv4-p-pro230 (accessed [today's date]).

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