Is FKBP14 p.Gly72Asp (c.215G>A) pathogenic?

FKBP14 p.Gly72Asp (c.215G>A) is classified Uncertain significance in FKBP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-28). AlphaMissense: ambiguous (0.3806); Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Gly72Asp (c.215G>A)?

FKBP14 p.Gly72Asp (c.215G>A) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Gly72Asp (c.215G>A) in the general population?

FKBP14 p.Gly72Asp (c.215G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about FKBP14 p.Gly72Asp (c.215G>A)?

AlphaMissense predicts ambiguous (score 0.3806) — an in-silico prediction, not a clinical call.

FKBP14 p.Gly72Asp

c.215G>A · rs949937945 · VCV1786874

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3806	ambiguous
REVEL	0.274	benign-leaning
SaProt	LLR -6.86	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 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.00267% African / African-American · 2/75,000 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,600 alleles · very rare exomes 3/1,461,292 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,500
European (non-Finnish)	8.48e-05%	1,179,892

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.Gly72Asp
Coding: c.215G>A
MANE Select: NM_017946
dbSNP: rs949937945
Type: single nucleotide variant
Location: chr7:30022799 (GRCh38)

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

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-gly72asp (accessed [today's date]).

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