Is GHSR p.Ser308= (c.924C>G) pathogenic?

GHSR p.Ser308= (c.924C>G) is classified Conflicting classifications of pathogenicity in GHSR (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-11). Rare (popmax 0.247%, mid); Associated with short stature due to GHSR deficiency.

What condition is associated with GHSR p.Ser308= (c.924C>G)?

GHSR p.Ser308= (c.924C>G) is associated with short stature due to GHSR deficiency (ClinVar).

How common is GHSR p.Ser308= (c.924C>G) in the general population?

GHSR p.Ser308= (c.924C>G) is rare (popmax 0.247%, mid) (gnomAD).

How is Short stature due to GHSR deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GHSR p.Ser308=

c.924C>G · rs145560801 · VCV761566

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, mid)

Conditions

short stature due to GHSR deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.072	GERP -2.2, phastCons 0.7
Overall
CADD	6.353	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% Middle Eastern · 15/6,062 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00923% 149/1,614,122 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.247%	404
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0183%	5,457
Finnishnot grpmax-eligible	0.0109%	9,146
European (non-Finnish)	0.00856%	11,683
South Asian	0.0011%	91,076

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: GHSR
Protein: p.Ser308=
Coding: c.924C>G
MANE Select: NM_198407
dbSNP: rs145560801
Type: single nucleotide variant
Location: chr3:172445338 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB
Residue 308: an α-helix

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

Disease context

short stature due to GHSR deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Short stature due to GHSR deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GHSR p.Arg141Pro Uncertain significance ★★ ⚠ same condition
GHSR p.Arg206Pro Uncertain significance ★★ ⚠ same condition
GHSR p.Arg237Trp Uncertain significance ★★ ⚠ same condition
GHSR p.Leu42Val Uncertain significance ★★ ⚠ same condition
GHSR p.Lys259Asn Uncertain significance ★★ ⚠ same condition
GHSR p.Ser252Leu Uncertain significance ★★ ⚠ same condition
GHSR c.*114A>G Benign ★★ same condition
GHSR c.*122C>T Benign ★★ 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-ser308 (accessed [today's date]).

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