Is FKBP14 p.Ile187= (c.561T>A) pathogenic?

FKBP14 p.Ile187= (c.561T>A) is classified Likely benign in FKBP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-03). Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Ile187= (c.561T>A)?

FKBP14 p.Ile187= (c.561T>A) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Ile187= (c.561T>A) in the general population?

FKBP14 p.Ile187= (c.561T>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

FKBP14 p.Ile187=

c.561T>A · rs2127946638 · VCV1575555

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 3.9	GERP -0.57, phastCons 1
Overall
CADD	9.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,286 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,526 alleles · very rare exomes 3/1,459,282 · genomes 0/152,244 · joint denominator

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.Ile187=
Coding: c.561T>A
MANE Select: NM_017946
dbSNP: rs2127946638
Type: single nucleotide variant
Location: chr7:30014810 (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 187: an α-helix; the ef-hand 2 domain

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

Similar variants

FKBP14 p.Ile187Ser Uncertain significance ★★ ⚠ same residue
FKBP14 p.Ile187Val 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

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-ile187 (accessed [today's date]).

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