Is FKBP14 p.Leu10Phe (c.30G>C) pathogenic?

FKBP14 p.Leu10Phe (c.30G>C) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-05). AlphaMissense: likely benign (0.0544); Very rare (popmax 0.00134%, afr); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2.

What condition is associated with FKBP14 p.Leu10Phe (c.30G>C)?

FKBP14 p.Leu10Phe (c.30G>C) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Leu10Phe (c.30G>C) in the general population?

FKBP14 p.Leu10Phe (c.30G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about FKBP14 p.Leu10Phe (c.30G>C)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

FKBP14 p.Leu10Phe

c.30G>C · rs1473185753 · VCV1024756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

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	0.0544	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP -0.39, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	9.115	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 0.00134% African / African-American · 1/74,848 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,612,826 alleles · very rare exomes 9/1,460,614 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,848
European (non-Finnish)	0.000848%	117,960

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.Leu10Phe
Coding: c.30G>C
MANE Select: NM_017946
dbSNP: rs1473185753
Type: single nucleotide variant
Location: chr7:30026479 (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-leu10phe (accessed [today's date]).

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