Is GPR68 p.Ala38= (c.114C>T) pathogenic?

GPR68 p.Ala38= (c.114C>T) is classified Benign in GPR68 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-12). Common (popmax 7.48%, sas) — too common for a highly-penetrant pathogenic allele.

GPR68 p.Ala38=

Q: How common is GPR68 p.Ala38= (c.114C>T) in the general population?

GPR68 p.Ala38= (c.114C>T) is common (popmax 7.48%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.114C>T · rs184986403 · VCV1181225

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.48%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 2.2, phastCons 1
Overall
CADD	18.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.48% South Asian · 6,811/91,036 alleles

Filtering AF 7.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.27%

Overall 1.01% 16,321/1,614,078 alleles · common exomes 14,730/1,461,738 · genomes 1,591/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	7.48%	13
East Asian	3.13%	32
Remaining individualsnot grpmax-eligible	1.41%	71
Middle Eastern	0.941%	106
Admixed American	0.823%	121
African / African-American	0.818%	122
Ashkenazi Jewishnot grpmax-eligible	0.787%	127
European (non-Finnish)	0.488%	205
Finnishnot grpmax-eligible	0.103%	970

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.Ala38=
Coding: c.114C>T
MANE Select: NM_001177676
dbSNP: rs184986403
Type: single nucleotide variant
Location: chr14:91234937 (GRCh38)
Gene constraint: LOEUF 1.154 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21 · 5 PDB
Residue 38: an α-helix

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

Similar variants

GPR68 p.Ala38Val Uncertain significance ★ ⚠ same residue
GPR68 p.Arg183= 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

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-ala38 (accessed [today's date]).

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