Is FKBP14 p.Leu109= (c.325C>T) pathogenic?

FKBP14 p.Leu109= (c.325C>T) is classified Likely benign in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2.

What condition is associated with FKBP14 p.Leu109= (c.325C>T)?

FKBP14 p.Leu109= (c.325C>T) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Leu109= (c.325C>T) in the general population?

FKBP14 p.Leu109= (c.325C>T) is absent from gnomAD v4.1 (gnomAD).

FKBP14 p.Leu109=

c.325C>T · rs2127949515 · VCV1568174

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type, 2

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 6.4	GERP 0.45, phastCons 1
Overall
CADD	8.721	PHRED · no single calibrated threshold — expert panels disagree

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: FKBP14
Protein: p.Leu109=
Coding: c.325C>T
MANE Select: NM_017946
dbSNP: rs2127949515
Type: single nucleotide variant
Location: chr7:30022689 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.27 · 2 PDB
Residue 109: the ppiase fkbp-type domain; an α-helix

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

Disease context

Ehlers-Danlos syndrome, kyphoscoliotic type, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Kyphoscoliotic Ehlers-Danlos syndrome (Orphanet):

Onset: Antenatal, Neonatal

Similar variants

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
FKBP14 p.Glu99Gln 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-leu109 (accessed [today's date]).

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