Is FKBP14 p.Ile126Val (c.376A>G) pathogenic?

FKBP14 p.Ile126Val (c.376A>G) is classified Uncertain significance in FKBP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.0854); Very rare (popmax 8.54e-05%, nfe).

How common is FKBP14 p.Ile126Val (c.376A>G) in the general population?

FKBP14 p.Ile126Val (c.376A>G) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about FKBP14 p.Ile126Val (c.376A>G)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

FKBP14 p.Ile126Val

c.376A>G · rs1789964659 · VCV1693949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	18.69	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 8.54e-05% European (non-Finnish) · 1/1,170,552 alleles

Overall 6.32e-05% 1/1,582,100 alleles · very rare exomes 1/1,429,818 · genomes 0/152,282 · 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.Ile126Val
Coding: c.376A>G
MANE Select: NM_017946
dbSNP: rs1789964659
Type: single nucleotide variant
Location: chr7:30019097 (GRCh38)

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

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-ile126val (accessed [today's date]).

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