Is FGF23 p.Ser20= (c.60C>T) pathogenic?

FGF23 p.Ser20= (c.60C>T) is classified Uncertain significance in FGF23 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00329%, sas); Associated with autosomal dominant hypophosphatemic rickets.

What condition is associated with FGF23 p.Ser20= (c.60C>T)?

FGF23 p.Ser20= (c.60C>T) is associated with autosomal dominant hypophosphatemic rickets, tumoral calcinosis, hyperphosphatemic, familial, 2 (ClinVar).

How common is FGF23 p.Ser20= (c.60C>T) in the general population?

FGF23 p.Ser20= (c.60C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Autosomal dominant hypophosphatemic rickets inherited?

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

FGF23 p.Ser20=

c.60C>T · rs763114180 · VCV882413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

autosomal dominant hypophosphatemic rickets

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 0.11	GERP -2.2
Overall
CADD	5.307	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,612,478 alleles · very rare exomes 8/1,460,124 · genomes 1/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
European (non-Finnish)	0.000508%	196,668

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.Ser20=
Coding: c.60C>T
MANE Select: NM_020638
dbSNP: rs763114180
Type: single nucleotide variant
Location: chr12:4379523 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 6 PDB

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

Disease context

autosomal dominant hypophosphatemic rickets — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tumoral calcinosis, hyperphosphatemic, familial, 2

For Autosomal dominant hypophosphatemic rickets (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

FGF23 p.Ser20Gly Uncertain significance ★ ⚠ same residue
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

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-ser20 (accessed [today's date]).

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