Is PTH p.Val33Glu (c.98T>A) pathogenic?

PTH p.Val33Glu (c.98T>A) is classified Uncertain significance in PTH (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.912); Absent from gnomAD v4.1; Associated with hypoparathyroidism, familial isolated 1.

What condition is associated with PTH p.Val33Glu (c.98T>A)?

PTH p.Val33Glu (c.98T>A) is associated with hypoparathyroidism, familial isolated 1 (ClinVar).

How common is PTH p.Val33Glu (c.98T>A) in the general population?

PTH p.Val33Glu (c.98T>A) 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.Val33Glu (c.98T>A)?

AlphaMissense predicts likely pathogenic (score 0.912) — an in-silico prediction, not a clinical call.

PTH p.Val33Glu

c.98T>A · rs2499939905 · VCV2627520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.912 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypoparathyroidism, familial isolated 1

Computational evidence

Protein change
AlphaMissense	0.912	likely pathogenic · top 3% in PTH
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 447 bp · p 0.43 · regional, not allelic
Overall
CADD	26.2	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.Val33Glu
Coding: c.98T>A
MANE Select: NM_000315
dbSNP: rs2499939905
Type: single nucleotide variant
Location: chr11:13492655 (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.Ser32Pro Likely pathogenic ★ ⚠ same condition
PTH p.Arg56His Uncertain significance ★ ⚠ same condition
PTH p.Gly43Glu 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-val33glu (accessed [today's date]).

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