Is FKBP14 p.His171Arg (c.512A>G) pathogenic?

FKBP14 p.His171Arg (c.512A>G) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). AlphaMissense: likely benign (0.2188); Very rare (popmax 8.5e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.His171Arg (c.512A>G)?

FKBP14 p.His171Arg (c.512A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is FKBP14 p.His171Arg (c.512A>G) in the general population?

FKBP14 p.His171Arg (c.512A>G) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about FKBP14 p.His171Arg (c.512A>G)?

AlphaMissense predicts likely benign (score 0.2188) — an in-silico prediction, not a clinical call.

FKBP14 p.His171Arg

c.512A>G · rs147665999 · VCV1745524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2188	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	24.4	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 8.5e-05% European (non-Finnish) · 1/1,176,122 alleles

Overall 6.26e-05% 1/1,598,444 alleles · very rare exomes 1/1,446,180 · genomes 0/152,264 · joint denominator

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.His171Arg
Coding: c.512A>G
MANE Select: NM_017946
dbSNP: rs147665999
Type: single nucleotide variant
Location: chr7:30014859 (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.His171Tyr Uncertain significance ★ ⚠ 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-his171arg (accessed [today's date]).

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