Is GHSR p.Ser123Arg (c.367A>C) pathogenic?

GHSR p.Ser123Arg (c.367A>C) is classified Uncertain significance in GHSR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely pathogenic (0.9808); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GHSR p.Ser123Arg (c.367A>C)?

GHSR p.Ser123Arg (c.367A>C) is associated with Inborn genetic diseases (ClinVar).

How common is GHSR p.Ser123Arg (c.367A>C) in the general population?

GHSR p.Ser123Arg (c.367A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GHSR p.Ser123Arg (c.367A>C)?

AlphaMissense predicts likely pathogenic (score 0.9808) — an in-silico prediction, not a clinical call.

GHSR p.Ser123Arg

c.367A>C · rs142733811 · VCV2474012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9808 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9808	likely pathogenic · top 8% in GHSR
REVEL	0.35	indeterminate
SaProt	LLR -4.62	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 6.2	GERP 0.75, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,249 bp · p 0.34 · regional, not allelic
Overall
CADD	26.2	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.Ser123Arg
Coding: c.367A>C
MANE Select: NM_198407
dbSNP: rs142733811
Type: single nucleotide variant
Location: chr3:172448047 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB
Residue 123: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GHSR p.Ser123Gly Uncertain significance ★★ ⚠ same residue
GHSR p.Arg141Pro Uncertain significance ★★ ⚠ same condition
GHSR p.Ile58Met Uncertain significance ★★ ⚠ same condition
GHSR p.Leu274Phe Uncertain significance ★★ ⚠ same condition
GHSR p.Phe220Cys Uncertain significance ★★ ⚠ same condition
GHSR p.Thr229Met Uncertain significance ★★ ⚠ same condition
GHSR p.Thr49Ile Uncertain significance ★★ ⚠ same condition
GHSR p.Thr64Ser Uncertain significance ★★ ⚠ same condition

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-ser123arg (accessed [today's date]).

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