Is GPR68 p.Ser290= (c.870C>T) pathogenic?

GPR68 p.Ser290= (c.870C>T) is classified Likely benign in GPR68 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-09). Rare (popmax 0.284%, nfe); Associated with GPR68-related disorder.

What condition is associated with GPR68 p.Ser290= (c.870C>T)?

GPR68 p.Ser290= (c.870C>T) is associated with GPR68-related disorder (ClinVar).

How common is GPR68 p.Ser290= (c.870C>T) in the general population?

GPR68 p.Ser290= (c.870C>T) is rare (popmax 0.284%, nfe) (gnomAD).

GPR68 p.Ser290=

c.870C>T · rs117875989 · VCV3038180

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.284%, nfe)

Conditions

GPR68-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.4	GERP -4.6
Overall
CADD	2.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.284% European (non-Finnish) · 3,270/1,150,714 alleles

Filtering AF 0.276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.273%

Overall 0.222% 3,445/1,548,510 alleles · rare exomes 3,176/1,396,134 · genomes 269/152,376 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.284%	352
Remaining individualsnot grpmax-eligible	0.131%	763
Finnishnot grpmax-eligible	0.114%	878
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0395%	2,535
Admixed American	0.0136%	7,379
Ashkenazi Jewishnot grpmax-eligible	0.0035%	28,540

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: GPR68
Protein: p.Ser290=
Coding: c.870C>T
MANE Select: NM_001177676
dbSNP: rs117875989
Type: single nucleotide variant
Location: chr14:91234181 (GRCh38)
Gene constraint: LOEUF 1.154 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21 · 5 PDB

Full GPR68 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPR68-related disorder

Similar variants

GPR68 p.Ala281= Likely benign same condition
GPR68 p.Cys114= Likely benign same condition
GPR68 p.Phe45= Likely benign same condition
GPR68 p.Ser73= Likely benign same condition
GPR68 p.Tyr120= Likely benign same condition
GPR68 p.Val141= Likely benign same condition
GPR68 p.Ala38= Benign ★★ same type
GPR68 p.Arg183= Benign ★★ 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/gpr68-p-ser290 (accessed [today's date]).

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