Is FKBP14 p.Val175= (c.525G>T) pathogenic?

FKBP14 p.Val175= (c.525G>T) is classified Conflicting classifications of pathogenicity in FKBP14 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0262%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Val175= (c.525G>T)?

FKBP14 p.Val175= (c.525G>T) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome (ClinVar).

How common is FKBP14 p.Val175= (c.525G>T) in the general population?

FKBP14 p.Val175= (c.525G>T) is ultra-rare (popmax 0.0262%, nfe) (gnomAD).

FKBP14 p.Val175=

c.525G>T · rs747381671 · VCV681733

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, nfe)

Conditions

Cardiovascular phenotype

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 -0.063	GERP -0.037, phastCons 0.6
Overall
CADD	6.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0262% European (non-Finnish) · 308/1,177,702 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0201% 323/1,604,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0262%	3,824
Admixed American	0.0123%	8,141
Remaining individualsnot grpmax-eligible	0.0113%	8,870
African / African-American	0.00134%	74,430

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: FKBP14
Protein: p.Val175=
Coding: c.525G>T
MANE Select: NM_017946
dbSNP: rs747381671
Type: single nucleotide variant
Location: chr7:30014846 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.27 · 2 PDB

Full FKBP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Ehlers-Danlos syndrome

Similar variants

FKBP14 p.Val175Glu Uncertain significance ★ ⚠ same residue
FKBP14 p.Ser143Ter Pathogenic/Likely pathogenic ★★ same condition
FKBP14 c.198-3T>C Uncertain significance ★★ same condition
FKBP14 p.Arg135Gln Uncertain significance ★★ ⚠ same condition
FKBP14 p.Arg2Ser Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp181Glu Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp46Gly Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp46Tyr 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/fkbp14-p-val175 (accessed [today's date]).

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