Is TRPV4 p.Phe485= (c.1455C>T) pathogenic?

TRPV4 p.Phe485= (c.1455C>T) is classified Benign/Likely benign in TRPV4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-25). Ultra-rare (popmax 0.0274%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRPV4 p.Phe485= (c.1455C>T)?

TRPV4 p.Phe485= (c.1455C>T) is associated with Inborn genetic diseases, autosomal dominant brachyolmia, metatropic dysplasia (ClinVar).

How common is TRPV4 p.Phe485= (c.1455C>T) in the general population?

TRPV4 p.Phe485= (c.1455C>T) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

TRPV4 p.Phe485=

c.1455C>T · rs189872222 · VCV307130

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

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 -0.12	GERP -4.3, phastCons 0.071
Overall
CADD	7.153	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,086 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00236% 38/1,613,414 alleles · ultra-rare exomes 29/1,461,068 · genomes 9/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
East Asian	0.0156%	6,411
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00333%	30,017

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.Phe485=
Coding: c.1455C>T
MANE Select: NM_021625
dbSNP: rs189872222
Type: single nucleotide variant
Location: chr12:109794365 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 19 PDB
Residue 485: 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: autosomal dominant brachyolmia metatropic dysplasia scapuloperoneal spinal muscular atrophy, autosomal dominant spondylometaphyseal dysplasia, Kozlowski type neuronopathy, distal hereditary motor, autosomal dominant 8 Charcot-Marie-Tooth disease axonal type 2C

Similar variants

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
TRPV4 p.Arg315Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRPV4 p.Arg316Cys Pathogenic ★★ ⚠ same condition
TRPV4 p.Arg316His 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-phe485 (accessed [today's date]).

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