Is PTH p.Arg83= (c.247C>A) pathogenic?

PTH p.Arg83= (c.247C>A) is classified Benign/Likely benign in PTH (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 31.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with hypoparathyroidism, familial isolated 1.

What condition is associated with PTH p.Arg83= (c.247C>A)?

PTH p.Arg83= (c.247C>A) is associated with hypoparathyroidism, familial isolated 1, 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.Arg83=

Q: How common is PTH p.Arg83= (c.247C>A) in the general population?

PTH p.Arg83= (c.247C>A) is common (popmax 31.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.247C>A · rs6256 · VCV255817

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 31.9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

hypoparathyroidism, familial isolated 1

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 0.31	GERP -4.6
Overall
CADD	4.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.9% South Asian · 29,087/91,040 alleles

Filtering AF 31.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.5%

Overall 15.6% 252,047/1,613,284 alleles · common exomes 232,296/1,461,802 · genomes 19,751/151,482 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	31.9%	3
Middle Eastern	23.6%	4
Ashkenazi Jewishnot grpmax-eligible	20%	5
Remaining individualsnot grpmax-eligible	16.4%	6
European (non-Finnish)	15.3%	7
Finnishnot grpmax-eligible	13.9%	7
East Asian	11.4%	9
Admixed American	9.05%	11
African / African-American	6.65%	15
Amishnot grpmax-eligible	5.38%	19

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.Arg83=
Coding: c.247C>A
MANE Select: NM_000315
dbSNP: rs6256
Type: single nucleotide variant
Location: chr11:13492506 (GRCh38)
Gene constraint: LOEUF 1.32 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 72.93 · 26 PDB
Residue 83: the 'disordered' region

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

Also linked: familial hypoparathyroidism

For Familial isolated hypoparathyroidism (Orphanet):

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

Similar variants

PTH p.Arg83Ter Likely 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.Glu92= Benign ★★ same condition
PTH p.Cys18Arg Likely pathogenic ★ same condition
PTH p.Ser32Pro 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-arg83 (accessed [today's date]).

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