Is PTH p.Glu92= (c.276G>A) pathogenic?

PTH p.Glu92= (c.276G>A) is classified Benign in PTH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). Common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele; Associated with familial hypoparathyroidism.

What condition is associated with PTH p.Glu92= (c.276G>A)?

PTH p.Glu92= (c.276G>A) is associated with familial hypoparathyroidism (ClinVar).

How is Familial isolated hypoparathyroidism inherited?

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

PTH p.Glu92=

Q: How common is PTH p.Glu92= (c.276G>A) in the general population?

PTH p.Glu92= (c.276G>A) is common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.276G>A · rs76760723 · VCV303703

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.02%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.36	GERP -4.6
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.02% African / African-American · 3,765/75,032 alleles

Filtering AF 4.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.83%

Overall 0.258% 4,167/1,614,114 alleles · common exomes 2,039/1,461,838 · genomes 2,128/152,276 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.02%	20
Remaining individualsnot grpmax-eligible	0.283%	353
Admixed American	0.258%	387
Middle Eastern	0.0825%	1,212
South Asian	0.00878%	11,385
European (non-Finnish)	0.00483%	20,702

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.Glu92=
Coding: c.276G>A
MANE Select: NM_000315
dbSNP: rs76760723
Type: single nucleotide variant
Location: chr11:13492477 (GRCh38)
Gene constraint: LOEUF 1.32 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 72.93 · 26 PDB
Residue 92: the 'disordered' region

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.Glu92Ala Uncertain significance ★ ⚠ 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.Arg83Ter Likely pathogenic ★ same condition
PTH c.*55C>T 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/pth-p-glu92 (accessed [today's date]).

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