Is GNAS p.Ser187= (c.561C>T) pathogenic?

GNAS p.Ser187= (c.561C>T) is classified Likely benign in GNAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Very rare (popmax 0.00769%, sas).

How common is GNAS p.Ser187= (c.561C>T) in the general population?

GNAS p.Ser187= (c.561C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

GNAS p.Ser187=

c.561C>T · VCV3905560

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.4, phastCons 1
Overall
CADD	11.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,028 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000436% 7/1,605,198 alleles · very rare exomes 6/1,453,064 · genomes 1/152,134 · joint denominator

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: GNAS
Protein: p.Ser187=
Coding: c.561C>T
MANE Select: NM_000516 · reported on NM_016592
Type: single nucleotide variant
Location: chr20:58840667 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.47 · 200 PDB
Residue 187: the 'disordered' region; the g-alpha domain

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

Similar variants

GNAS p.Gln187Ter Pathogenic ★ same residue
GNAS p.Gln187Arg Uncertain significance ★ same residue
GNAS c.139+1G>C Pathogenic ★★ same type
GNAS c.139+2T>C Pathogenic ★★ same type
GNAS c.312+5G>A Pathogenic ★★ same type
GNAS c.432+1G>A Pathogenic ★★ same type
GNAS c.433-2A>C Pathogenic/Likely pathogenic ★★ same type
GNAS p.Ala102Thr Pathogenic/Likely pathogenic ★★ same type

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/gnas-p-ser187 (accessed [today's date]).

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