Is FKBP14 p.Asp46Val (c.137A>T) pathogenic?

FKBP14 p.Asp46Val (c.137A>T) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely pathogenic (0.9933); Very rare (popmax 0.00134%, afr).

How common is FKBP14 p.Asp46Val (c.137A>T) in the general population?

FKBP14 p.Asp46Val (c.137A>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about FKBP14 p.Asp46Val (c.137A>T)?

AlphaMissense predicts likely pathogenic (score 0.9933) — an in-silico prediction, not a clinical call.

FKBP14 p.Asp46Val

c.137A>T · VCV3769818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9933	likely pathogenic · top 3% in FKBP14
REVEL	0.679	pathogenic-leaning
SaProt	LLR -14.03	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 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00134% African / African-American · 1/74,890 alleles

Overall 6.2e-05% 1/1,613,958 alleles · very rare exomes 0/1,461,836 · genomes 1/152,122 · 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.Asp46Val
Coding: c.137A>T
MANE Select: NM_017946
Type: single nucleotide variant
Location: chr7:30026372 (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 46: the ppiase fkbp-type domain

Full FKBP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FKBP14 p.Asp46Gly Uncertain significance ★★ ⚠ same residue
FKBP14 p.Asp46Tyr Uncertain significance ★★ ⚠ same residue
FKBP14 p.Ser143Ter Pathogenic/Likely pathogenic ★★ same type
FKBP14 c.198-3T>C Uncertain significance ★★ same type
FKBP14 p.Arg135Gln Uncertain significance ★★ ⚠ same type
FKBP14 p.Arg2Ser Uncertain significance ★★ ⚠ same type
FKBP14 p.Asp181Glu Uncertain significance ★★ ⚠ same type
FKBP14 p.Glu99Gln 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/fkbp14-p-asp46val (accessed [today's date]).

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