Is GCM2 p.Ser62= (c.186C>T) pathogenic?

GCM2 p.Ser62= (c.186C>T) is classified Benign/Likely benign in GCM2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Low-frequency (popmax 1.69%, eas); Associated with familial hypoparathyroidism.

What condition is associated with GCM2 p.Ser62= (c.186C>T)?

GCM2 p.Ser62= (c.186C>T) is associated with familial hypoparathyroidism (ClinVar).

How common is GCM2 p.Ser62= (c.186C>T) in the general population?

GCM2 p.Ser62= (c.186C>T) is low-frequency (popmax 1.69%, eas) (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.Ser62=

c.186C>T · rs141006427 · VCV355019

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.69%, eas)

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 -0.63	GERP -1.9, phastCons 0.001
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.69% East Asian · 760/44,870 alleles

Filtering AF 1.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.55%

Overall 0.0651% 1,051/1,614,198 alleles · low-frequency exomes 985/1,461,886 · genomes 66/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.69%	59
South Asian	0.101%	990
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0183%	5,457
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.011%	9,077
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00266%	37,529

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.Ser62=
Coding: c.186C>T
MANE Select: NM_004752
dbSNP: rs141006427
Type: single nucleotide variant
Location: chr6:10877297 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.78
Residue 62: a DNA-binding region

Full GCM2 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

GCM2 c.90+2T>G Likely pathogenic ★★ same condition
GCM2 p.Tyr136Ter Pathogenic ★★ same condition
GCM2 c.*217T>A Uncertain significance ★★ same condition
GCM2 p.Ala355Thr Uncertain significance ★★ ⚠ same condition
GCM2 p.Arg143Gln Uncertain significance ★★ ⚠ same condition
GCM2 p.Arg39Gln Uncertain significance ★★ ⚠ same condition
GCM2 p.Arg455Gln Uncertain significance ★★ ⚠ same condition
GCM2 p.Asn502His 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-ser62 (accessed [today's date]).

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