Is FKBP14 p.Trp88Ser (c.263G>C) pathogenic?

FKBP14 p.Trp88Ser (c.263G>C) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.9833); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Trp88Ser (c.263G>C)?

FKBP14 p.Trp88Ser (c.263G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is FKBP14 p.Trp88Ser (c.263G>C) in the general population?

FKBP14 p.Trp88Ser (c.263G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FKBP14 p.Trp88Ser (c.263G>C)?

AlphaMissense predicts likely pathogenic (score 0.9833) — an in-silico prediction, not a clinical call.

FKBP14 p.Trp88Ser

c.263G>C · VCV3850477

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9833	likely pathogenic · top 8% in FKBP14
REVEL	0.724	pathogenic-leaning
SaProt	LLR -13.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Trp88Ser
Coding: c.263G>C
MANE Select: NM_017946
Type: single nucleotide variant
Location: chr7:30022751 (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 88: the ppiase fkbp-type domain; an α-helix

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.Trp88Ter Pathogenic ★ 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
FKBP14 p.Gly60Asp Uncertain significance ★★ ⚠ same condition
FKBP14 p.His179Gln Uncertain significance ★★ ⚠ same condition
FKBP14 p.His69Arg 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-trp88ser (accessed [today's date]).

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