Is FGF23 p.Val83= (c.249G>A) pathogenic?

FGF23 p.Val83= (c.249G>A) is classified Conflicting classifications of pathogenicity in FGF23 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-25). Rare (popmax 0.475%, eas); Associated with tumoral calcinosis, hyperphosphatemic, familial, 2.

What condition is associated with FGF23 p.Val83= (c.249G>A)?

FGF23 p.Val83= (c.249G>A) is associated with tumoral calcinosis, hyperphosphatemic, familial, 2, autosomal dominant hypophosphatemic rickets (ClinVar).

How common is FGF23 p.Val83= (c.249G>A) in the general population?

FGF23 p.Val83= (c.249G>A) is rare (popmax 0.475%, eas) (gnomAD).

How is Familial tumoral calcinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FGF23 p.Val83=

c.249G>A · rs753676774 · VCV882162

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.475%, eas)

Conditions

tumoral calcinosis, hyperphosphatemic, familial, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP 1.9, phastCons 1
Overall
CADD	9.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.475% East Asian · 213/44,876 alleles

Filtering AF 0.422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.0135% 218/1,613,770 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.475%	211
Admixed American	0.00167%	60,026
European (non-Finnish)	0.000339%	294,924

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: FGF23
Protein: p.Val83=
Coding: c.249G>A
MANE Select: NM_020638
dbSNP: rs753676774
Type: single nucleotide variant
Location: chr12:4372660 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 6 PDB
Residue 83: a β-strand

Full FGF23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tumoral calcinosis, hyperphosphatemic, familial, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant hypophosphatemic rickets

For Familial tumoral calcinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

FGF23 p.Arg179Gln Pathogenic ★★ ⚠ same condition
FGF23 p.Arg179Trp Pathogenic/Likely pathogenic ★★ same condition
FGF23 p.Gln54His Likely pathogenic ★★ ⚠ same condition
FGF23 p.Ser129Pro Pathogenic/Likely pathogenic ★★ same condition
FGF23 p.Ala213Thr Uncertain significance ★★ ⚠ same condition
FGF23 p.Ala236Pro Uncertain significance ★★ ⚠ same condition
FGF23 p.Ala45Thr Uncertain significance ★★ ⚠ same condition
FGF23 p.Arg187Trp 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/fgf23-p-val83 (accessed [today's date]).

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