Is GPR39 p.Ser347Phe (c.1040C>T) pathogenic?

GPR39 p.Ser347Phe (c.1040C>T) is classified Uncertain significance in GPR39 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely pathogenic (0.8462); Very rare (popmax 0.00133%, afr).

How common is GPR39 p.Ser347Phe (c.1040C>T) in the general population?

GPR39 p.Ser347Phe (c.1040C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about GPR39 p.Ser347Phe (c.1040C>T)?

AlphaMissense predicts likely pathogenic (score 0.8462) — an in-silico prediction, not a clinical call.

GPR39 p.Ser347Phe

c.1040C>T · rs140279287 · VCV2621004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8462	likely pathogenic
REVEL	0.289	benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 228 kb · p 0.00098 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.00133% African / African-American · 1/75,070 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,246 alleles · very rare exomes 1/1,461,894 · genomes 4/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,070
European (non-Finnish)	0.000339%	295,012

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.Ser347Phe
Coding: c.1040C>T
MANE Select: NM_001508
dbSNP: rs140279287
Type: single nucleotide variant
Location: chr2:132645284 (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-ser347phe (accessed [today's date]).

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