Is FKBP3 p.Ile172Phe (c.514A>T) pathogenic?

FKBP3 p.Ile172Phe (c.514A>T) is classified Uncertain significance in FKBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely pathogenic (0.9916); Very rare (popmax 0.0028%, nfe).

How common is FKBP3 p.Ile172Phe (c.514A>T) in the general population?

FKBP3 p.Ile172Phe (c.514A>T) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about FKBP3 p.Ile172Phe (c.514A>T)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

FKBP3 p.Ile172Phe

c.514A>T · rs369567635 · VCV2479868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -13.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 0.19 · regional, not allelic
Overall
CADD	29.9	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

Grpmax group 0.0028% European (non-Finnish) · 33/1,179,214 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00211% 34/1,612,668 alleles · very rare exomes 33/1,460,464 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,734
Remaining individualsnot grpmax-eligible	0.0016%	62,440

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: FKBP3
Protein: p.Ile172Phe
Coding: c.514A>T
MANE Select: NM_002013
dbSNP: rs369567635
Type: single nucleotide variant
Location: chr14:45120895 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 5 PDB
Residue 172: the ppiase fkbp-type domain

Full FKBP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FKBP3 p.Arg16His Uncertain significance ★ ⚠ same type
FKBP3 p.Arg189Gln Uncertain significance ★ ⚠ same type
FKBP3 p.Arg8Trp Uncertain significance ★ ⚠ same type
FKBP3 p.Asp205Tyr Uncertain significance ★ ⚠ same type
FKBP3 p.Asp57Gly Uncertain significance ★ ⚠ same type
FKBP3 p.Glu102Asp Uncertain significance ★ ⚠ same type
FKBP3 p.Glu217Ala Uncertain significance ★ ⚠ same type
FKBP3 p.Glu92Asp Uncertain significance ★ ⚠ same type

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/fkbp3-p-ile172phe (accessed [today's date]).

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