Is PTH p.Ser23= (c.69G>A) pathogenic?

PTH p.Ser23= (c.69G>A) is classified Benign in PTH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0178%, eas); Associated with familial hypoparathyroidism.

What condition is associated with PTH p.Ser23= (c.69G>A)?

PTH p.Ser23= (c.69G>A) is associated with familial hypoparathyroidism (ClinVar).

How common is PTH p.Ser23= (c.69G>A) in the general population?

PTH p.Ser23= (c.69G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

How is Familial isolated hypoparathyroidism inherited?

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

PTH p.Ser23=

c.69G>A · rs377308600 · VCV880247

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

familial hypoparathyroidism

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 -4.1	GERP -4.6
Overall
CADD	6.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,884 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00149% 24/1,613,778 alleles · ultra-rare exomes 20/1,461,670 · genomes 4/152,108 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
Remaining individualsnot grpmax-eligible	0.0032%	31,238
Admixed American	0.00167%	59,916
African / African-American	0.00134%	74,884
European (non-Finnish)	0.00102%	98,329

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: PTH
Protein: p.Ser23=
Coding: c.69G>A
MANE Select: NM_000315
dbSNP: rs377308600
Type: single nucleotide variant
Location: chr11:13492787 (GRCh38)
Gene constraint: LOEUF 1.32 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 72.93 · 26 PDB
Residue 23: a UniProt-annotated variant site (in fih1; recessive form; might lead to inefficient processing of the precursor)

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

Disease context

familial hypoparathyroidism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial isolated hypoparathyroidism (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages

Similar variants

PTH p.Ser23Pro Pathogenic ⚠ same residue
PTH c.-33C>T Uncertain significance ★★ same condition
PTH c.86+9T>G Benign ★★ same condition
PTH c.-5-10G>A Benign/Likely benign ★★ same condition
PTH c.*319A>G Benign ★★ same condition
PTH p.Arg83= Benign/Likely benign ★★ same condition
PTH p.Glu92= Benign ★★ same condition
PTH p.Arg83Ter Likely pathogenic ★ 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/pth-p-ser23 (accessed [today's date]).

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