Is FKBP14 p.Lys166del (c.493AAG[1]) pathogenic?

FKBP14 p.Lys166del (c.493AAG[1]) is classified Conflicting classifications of pathogenicity in FKBP14 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-06-10). Rare (popmax 0.18%, sas); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Lys166del (c.493AAG[1])?

FKBP14 p.Lys166del (c.493AAG[1]) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome (ClinVar).

How common is FKBP14 p.Lys166del (c.493AAG[1]) in the general population?

FKBP14 p.Lys166del (c.493AAG[1]) is rare (popmax 0.18%, sas) (gnomAD).

FKBP14 p.Lys166del

c.493AAG[1] · rs542254849 · VCV432169

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.18%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.18% South Asian · 156/86,552 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.136% 2,165/1,594,244 alleles · rare exomes 2,015/1,442,052 · genomes 150/152,192 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.234%	428
South Asiangrpmax	0.18%	555
European (non-Finnish)	0.153%	655
Remaining individualsnot grpmax-eligible	0.122%	822
Middle Eastern	0.117%	852
Admixed American	0.0425%	2,354
Finnishnot grpmax-eligible	0.0332%	3,016
African / African-American	0.0325%	3,081

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys166del
Coding: c.493AAG[1]
MANE Select: NM_017946
dbSNP: rs542254849
Type: Microsatellite
Location: chr7:30014873 (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 166: the ef-hand 1 domain; an α-helix

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 c.197+5_197+8del Likely pathogenic ★ same condition
FKBP14 p.Asn176fs Likely pathogenic ★ same condition
FKBP14 p.Leu12fs Pathogenic ★ same condition
FKBP14 p.Leu32fs Pathogenic ★ same condition
FKBP14 p.Leu155_Ser156insTer Conflicting classifications of pathogenicity ★ same condition
FKBP14 p.Ter212GluextTer? Uncertain significance ★ same condition
FKBP14 c.477+15_477+17del Likely benign ★ same condition
FKBP14 p.Glu191del 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/fkbp14-p-lys166del (accessed [today's date]).

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