Is FKBP14 p.Ile129Val (c.385A>G) pathogenic?

FKBP14 p.Ile129Val (c.385A>G) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-30). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00137%, afr); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2.

What condition is associated with FKBP14 p.Ile129Val (c.385A>G)?

FKBP14 p.Ile129Val (c.385A>G) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Ile129Val (c.385A>G) in the general population?

FKBP14 p.Ile129Val (c.385A>G) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about FKBP14 p.Ile129Val (c.385A>G)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

FKBP14 p.Ile129Val

c.385A>G · rs771396716 · VCV1428787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type, 2

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	15.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,034 alleles

Overall 6.3e-05% 1/1,588,074 alleles · very rare exomes 1/1,435,806 · genomes 0/152,268 · 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.Ile129Val
Coding: c.385A>G
MANE Select: NM_017946
dbSNP: rs771396716
Type: single nucleotide variant
Location: chr7:30019088 (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 129: the ppiase fkbp-type domain; a β-strand

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.Ile129Thr 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-ile129val (accessed [today's date]).

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