Is FKBP14 p.Tyr111= (c.333T>C) pathogenic?

FKBP14 p.Tyr111= (c.333T>C) is classified Likely benign in FKBP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-20). Very rare (popmax 0.00772%, sas); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Tyr111= (c.333T>C)?

FKBP14 p.Tyr111= (c.333T>C) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Tyr111= (c.333T>C) in the general population?

FKBP14 p.Tyr111= (c.333T>C) is very rare (popmax 0.00772%, sas) (gnomAD).

FKBP14 p.Tyr111=

c.333T>C · rs564024029 · VCV1632353

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00772%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.82	GERP -0.024, phastCons 0.97
Overall
CADD	5.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00772% South Asian · 7/90,652 alleles

Filtering AF 0.0036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.00105% 17/1,612,290 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00772%	12,950
European (non-Finnish)	0.000848%	117,943

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.Tyr111=
Coding: c.333T>C
MANE Select: NM_017946
dbSNP: rs564024029
Type: single nucleotide variant
Location: chr7:30022681 (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 111: the ppiase fkbp-type domain; a turn

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.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-tyr111 (accessed [today's date]).

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