Is FKBP14 p.Ile18Ser (c.53T>G) pathogenic?

FKBP14 p.Ile18Ser (c.53T>G) is classified Likely benign in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.0588); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Ile18Ser (c.53T>G)?

FKBP14 p.Ile18Ser (c.53T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is FKBP14 p.Ile18Ser (c.53T>G) in the general population?

FKBP14 p.Ile18Ser (c.53T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKBP14 p.Ile18Ser (c.53T>G)?

AlphaMissense predicts likely benign (score 0.0588) — an in-silico prediction, not a clinical call.

FKBP14 p.Ile18Ser

c.53T>G · VCV3515480

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0588	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -4.33	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 0.59, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	20.5	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.Ile18Ser
Coding: c.53T>G
MANE Select: NM_017946
Type: single nucleotide variant
Location: chr7:30026456 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.27 · 2 PDB

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

Similar variants

FKBP14 p.Ile18Asn Uncertain significance ★ ⚠ same residue
FKBP14 p.Ile18Phe Uncertain significance ★ ⚠ same residue
FKBP14 p.Ile18Val Uncertain significance ★ ⚠ same residue
FKBP14 p.Ile18= Likely benign ★ same residue
FKBP14 c.198-3T>C Uncertain significance ★★ same condition
FKBP14 p.Arg2Ser Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp181Glu Uncertain significance ★★ ⚠ same condition
FKBP14 p.Gly197Arg 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-ile18ser (accessed [today's date]).

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