Is GPR68 p.Arg183= (c.549C>T) pathogenic?

GPR68 p.Arg183= (c.549C>T) is classified Benign in GPR68 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). Common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele.

GPR68 p.Arg183=

Q: How common is GPR68 p.Arg183= (c.549C>T) in the general population?

GPR68 p.Arg183= (c.549C>T) is common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.549C>T · rs2540862 · VCV1286992

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele

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 -4.7	GERP -4.3
Overall
CADD	0.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.9% African / African-American · 21,648/75,000 alleles

Filtering AF 28.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.4%

Overall 3.03% 48,908/1,613,830 alleles · common exomes 34,238/1,461,570 · genomes 14,670/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	28.9%	3
East Asian	13.5%	7
South Asian	8.91%	11
Middle Eastern	6.55%	15
Ashkenazi Jewishnot grpmax-eligible	5.2%	19
Remaining individualsnot grpmax-eligible	4.55%	22
Admixed American	2.47%	41
Finnishnot grpmax-eligible	0.852%	117
European (non-Finnish)	0.533%	188

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.Arg183=
Coding: c.549C>T
MANE Select: NM_001177676
dbSNP: rs2540862
Type: single nucleotide variant
Location: chr14:91234502 (GRCh38)
Gene constraint: LOEUF 1.154 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21 · 5 PDB
Residue 183: a turn

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

Similar variants

GPR68 p.Ala38= Benign ★★ same type
GPR68 p.Lys330Asn Likely benign ★★ same type
GPR68 p.Ala138Thr Uncertain significance ★ ⚠ same type
GPR68 p.Ala180Glu Uncertain significance ★ ⚠ same type
GPR68 p.Ala180Val Uncertain significance ★ ⚠ same type
GPR68 p.Ala211Thr Uncertain significance ★ ⚠ same type
GPR68 p.Ala211Val Uncertain significance ★ ⚠ same type
GPR68 p.Ala281Thr Uncertain significance ★ ⚠ 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-arg183 (accessed [today's date]).

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