Is GPR68 p.Val280Phe (c.838G>T) pathogenic?

GPR68 p.Val280Phe (c.838G>T) is classified Uncertain significance in GPR68 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.6008); No allele count reported in gnomAD v4.1 (AN 1,561,516).

How common is GPR68 p.Val280Phe (c.838G>T) in the general population?

GPR68 p.Val280Phe (c.838G>T) is no allele count reported in gnomAD v4.1 (AN 1,561,516) (gnomAD).

What do computational predictors say about GPR68 p.Val280Phe (c.838G>T)?

AlphaMissense predicts likely pathogenic (score 0.6008) — an in-silico prediction, not a clinical call.

GPR68 p.Val280Phe

c.838G>T · VCV3855390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6008 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,561,516)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6008	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 0.055, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,094 bp · p 0.82 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,561,516). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GPR68
Protein: p.Val280Phe
Coding: c.838G>T
MANE Select: NM_001177676
Type: single nucleotide variant
Location: chr14:91234213 (GRCh38)
Gene constraint: LOEUF 1.154 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21 · 5 PDB
Residue 280: an α-helix

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

Similar variants

GPR68 p.Ala38= Benign ★★ same type
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-val280phe (accessed [today's date]).

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