Is FKBP14 p.Ala173Val (c.518C>T) pathogenic?

FKBP14 p.Ala173Val (c.518C>T) is classified Conflicting classifications of pathogenicity in FKBP14 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1256); Very rare (popmax 0.00406%, afr); Associated with Cardiovascular phenotype.

What condition is associated with FKBP14 p.Ala173Val (c.518C>T)?

FKBP14 p.Ala173Val (c.518C>T) is associated with Cardiovascular phenotype, Ehlers-Danlos syndrome, kyphoscoliotic type, 2 (ClinVar).

How common is FKBP14 p.Ala173Val (c.518C>T) in the general population?

FKBP14 p.Ala173Val (c.518C>T) is very rare (popmax 0.00406%, afr) (gnomAD).

What do computational predictors say about FKBP14 p.Ala173Val (c.518C>T)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

FKBP14 p.Ala173Val

c.518C>T · rs757164371 · VCV1036143

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00406%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -4.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.8 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00406% African / African-American · 3/73,982 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00268%

Overall 0.00325% 52/1,599,336 alleles · very rare exomes 48/1,447,564 · genomes 4/151,772 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00406%	24,661
European (non-Finnish)	0.00391%	25,567
Remaining individualsnot grpmax-eligible	0.00323%	30,943
South Asian	0.00114%	87,678

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.Ala173Val
Coding: c.518C>T
MANE Select: NM_017946
dbSNP: rs757164371
Type: single nucleotide variant
Location: chr7:30014853 (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

Also linked: Ehlers-Danlos syndrome, kyphoscoliotic type, 2

Similar variants

FKBP14 p.Ser143Ter Pathogenic/Likely pathogenic ★★ same condition
FKBP14 c.198-3T>C Uncertain significance ★★ same condition
FKBP14 p.Arg135Gln Uncertain significance ★★ ⚠ same condition
FKBP14 p.Arg2Ser Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp181Glu Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp46Gly Uncertain significance ★★ ⚠ same condition
FKBP14 p.Asp46Tyr Uncertain significance ★★ ⚠ same condition
FKBP14 p.Glu99Gln 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-ala173val (accessed [today's date]).

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