Is FGF23 p.Ser185= (c.555G>C) pathogenic?

FGF23 p.Ser185= (c.555G>C) is classified Benign/Likely benign in FGF23 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.35%, afr); Associated with autosomal dominant hypophosphatemic rickets.

What condition is associated with FGF23 p.Ser185= (c.555G>C)?

FGF23 p.Ser185= (c.555G>C) is associated with autosomal dominant hypophosphatemic rickets, tumoral calcinosis, hyperphosphatemic, familial, 2 (ClinVar).

How common is FGF23 p.Ser185= (c.555G>C) in the general population?

FGF23 p.Ser185= (c.555G>C) is low-frequency (popmax 1.35%, afr) (gnomAD).

How is Autosomal dominant hypophosphatemic rickets inherited?

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

FGF23 p.Ser185=

c.555G>C · rs115283398 · VCV308804

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, afr)

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 -3.3	GERP -3.8
Overall
CADD	0.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.35% African / African-American · 1,008/74,928 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0728% 1,174/1,613,322 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.35%	74
Remaining individualsnot grpmax-eligible	0.0976%	1,024
Admixed American	0.0917%	1,091
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.00398%	25,096
South Asian	0.0011%	91,044

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.Ser185=
Coding: c.555G>C
MANE Select: NM_020638
dbSNP: rs115283398
Type: single nucleotide variant
Location: chr12:4370544 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 6 PDB
Residue 185: the 'disordered' region

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.Ser185Leu 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-ser185 (accessed [today's date]).

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