Is FKBP14 p.Arg40His (c.119G>A) pathogenic?

FKBP14 p.Arg40His (c.119G>A) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-27). AlphaMissense: ambiguous (0.4538); Absent from gnomAD v4.1; Associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2.

What condition is associated with FKBP14 p.Arg40His (c.119G>A)?

FKBP14 p.Arg40His (c.119G>A) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Arg40His (c.119G>A) in the general population?

FKBP14 p.Arg40His (c.119G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKBP14 p.Arg40His (c.119G>A)?

AlphaMissense predicts ambiguous (score 0.4538) — an in-silico prediction, not a clinical call.

FKBP14 p.Arg40His

c.119G>A · rs1554371032 · VCV473000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4538 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type, 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4538	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -9.63	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

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

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.Arg40His
Coding: c.119G>A
MANE Select: NM_017946
dbSNP: rs1554371032
Type: single nucleotide variant
Location: chr7:30026390 (GRCh38)

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

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-arg40his (accessed [today's date]).

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