Is PTH p.Ser32Pro (c.94T>C) pathogenic?

PTH p.Ser32Pro (c.94T>C) is classified Likely pathogenic in PTH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-17). AlphaMissense: likely pathogenic (0.5784); Absent from gnomAD v4.1; Associated with hypoparathyroidism, familial isolated 1.

What condition is associated with PTH p.Ser32Pro (c.94T>C)?

PTH p.Ser32Pro (c.94T>C) is associated with hypoparathyroidism, familial isolated 1 (ClinVar).

How common is PTH p.Ser32Pro (c.94T>C) in the general population?

PTH p.Ser32Pro (c.94T>C) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated hypoparathyroidism inherited?

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

What do computational predictors say about PTH p.Ser32Pro (c.94T>C)?

AlphaMissense predicts likely pathogenic (score 0.5784) — an in-silico prediction, not a clinical call.

PTH p.Ser32Pro

c.94T>C · VCV4850355

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hypoparathyroidism, familial isolated 1

Computational evidence

Protein change
AlphaMissense	0.5784	likely pathogenic ✓ concordant with ClinVar
REVEL	0.557	indeterminate
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -1.5, phastCons 0.46
Regional constraint	o/e 0.93	unconstrained · MANE · 447 bp · p 0.43 · regional, not allelic
Overall
CADD	17.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTH
Protein: p.Ser32Pro
Coding: c.94T>C
MANE Select: NM_000315
Type: single nucleotide variant
Location: chr11:13492659 (GRCh38)
Gene constraint: LOEUF 1.32 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 72.93 · 26 PDB

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

Disease context

hypoparathyroidism, familial isolated 1 — 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 c.-5-10G>A Benign/Likely benign ★★ same condition
PTH p.Arg83= Benign/Likely benign ★★ same condition
PTH p.Cys18Arg Likely pathogenic ★ same condition
PTH p.Arg56His Uncertain significance ★ ⚠ same condition
PTH p.Gly43Glu Uncertain significance ★ same condition
PTH p.Val33Glu Uncertain significance ★ ⚠ same condition
PTH c.86+1G>C Pathogenic same condition
PTH p.Ser23Pro 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-ser32pro (accessed [today's date]).

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