Is GCM2 p.Arg102= (c.306G>A) pathogenic?

GCM2 p.Arg102= (c.306G>A) is classified Benign/Likely benign in GCM2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.484%, afr); Associated with hypoparathyroidism, familial isolated, 2.

What condition is associated with GCM2 p.Arg102= (c.306G>A)?

GCM2 p.Arg102= (c.306G>A) is associated with hypoparathyroidism, familial isolated, 2, hyperparathyroidism 4 (ClinVar).

How common is GCM2 p.Arg102= (c.306G>A) in the general population?

GCM2 p.Arg102= (c.306G>A) is rare (popmax 0.484%, afr) (gnomAD).

How is Familial isolated hypoparathyroidism inherited?

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

GCM2 p.Arg102=

c.306G>A · rs149143032 · VCV736761

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.484%, afr)

Conditions

hypoparathyroidism, familial isolated, 2

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 -2.5	GERP -3.6
Overall
CADD	5.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.484% African / African-American · 363/75,068 alleles

Filtering AF 0.443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.426%

Overall 0.024% 388/1,613,726 alleles · rare exomes 190/1,461,354 · genomes 198/152,372 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.484%	207
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Admixed American	0.00999%	10,006
European (non-Finnish)	0.000169%	590,019

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: GCM2
Protein: p.Arg102=
Coding: c.306G>A
MANE Select: NM_004752
dbSNP: rs149143032
Type: single nucleotide variant
Location: chr6:10877177 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.78
Residue 102: a DNA-binding region

Full GCM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoparathyroidism, familial isolated, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperparathyroidism 4

For Familial isolated hypoparathyroidism (Orphanet):

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

Similar variants

GCM2 p.Arg47Leu Pathogenic ★★ same condition
GCM2 p.Arg67Cys Likely pathogenic ★★ same condition
GCM2 p.Tyr136Ter Pathogenic ★★ same condition
GCM2 p.Ala148Val Uncertain significance ★★ ⚠ same condition
GCM2 p.Ala180Pro Uncertain significance ★★ ⚠ same condition
GCM2 p.Ala355Thr Uncertain significance ★★ ⚠ same condition
GCM2 p.Ala451Val Uncertain significance ★★ ⚠ same condition
GCM2 p.Ala488Thr 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/gcm2-p-arg102 (accessed [today's date]).

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