Is GPR39 p.Pro88Ser (c.262C>T) pathogenic?

GPR39 p.Pro88Ser (c.262C>T) is classified Uncertain significance in GPR39 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.7437); Very rare (popmax 8.47e-05%, nfe).

How common is GPR39 p.Pro88Ser (c.262C>T) in the general population?

GPR39 p.Pro88Ser (c.262C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about GPR39 p.Pro88Ser (c.262C>T)?

AlphaMissense predicts likely pathogenic (score 0.7437) — an in-silico prediction, not a clinical call.

GPR39 p.Pro88Ser

c.262C>T · VCV3855343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7437	likely pathogenic
REVEL	0.759	pathogenic-leaning
SaProt	LLR -12.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 228 kb · p 0.00098 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.2e-05% 1/1,614,144 alleles · very rare exomes 1/1,461,886 · genomes 0/152,258 · 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: GPR39
Protein: p.Pro88Ser
Coding: c.262C>T
MANE Select: NM_001508
Type: single nucleotide variant
Location: chr2:132417304 (GRCh38)
Gene constraint: LOEUF 1.645 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.53

Full GPR39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPR39 p.Asn212Ser Benign ★★ same type
GPR39 p.Ala277Gly Uncertain significance ★ ⚠ same type
GPR39 p.Ala437Ser Uncertain significance ★ ⚠ same type
GPR39 p.Arg278Thr Uncertain significance ★ ⚠ same type
GPR39 p.Arg386Gly Uncertain significance ★ ⚠ same type
GPR39 p.Asn434Ser Uncertain significance ★ ⚠ same type
GPR39 p.Asp10His Uncertain significance ★ ⚠ same type
GPR39 p.Asp383Glu 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/gpr39-p-pro88ser (accessed [today's date]).

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