Is GHSR p.Ser289Phe (c.866C>T) pathogenic?

GHSR p.Ser289Phe (c.866C>T) is classified Uncertain significance in GHSR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.7337); Absent from gnomAD v4.1.

How common is GHSR p.Ser289Phe (c.866C>T) in the general population?

GHSR p.Ser289Phe (c.866C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GHSR p.Ser289Phe (c.866C>T)?

AlphaMissense predicts likely pathogenic (score 0.7337) — an in-silico prediction, not a clinical call.

GHSR p.Ser289Phe

c.866C>T · rs750378561 · VCV1949226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7337 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7337	likely pathogenic
REVEL	0.508	indeterminate
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,249 bp · p 0.34 · regional, not allelic
Overall
CADD	28.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GHSR
Protein: p.Ser289Phe
Coding: c.866C>T
MANE Select: NM_198407
dbSNP: rs750378561
Type: single nucleotide variant
Location: chr3:172445396 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB

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

Similar variants

GHSR p.Arg141Leu Uncertain significance ★★ ⚠ same type
GHSR p.Arg141Pro Uncertain significance ★★ ⚠ same type
GHSR p.Arg206Pro Uncertain significance ★★ ⚠ same type
GHSR p.Arg237Trp Uncertain significance ★★ ⚠ same type
GHSR p.Arg283Ter Uncertain significance ★★ same type
GHSR p.Glu73Asp Uncertain significance ★★ ⚠ same type
GHSR p.Glu9Lys Uncertain significance ★★ ⚠ same type
GHSR p.Ile167Phe 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/ghsr-p-ser289phe (accessed [today's date]).

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