Is GHSR p.Asp28= (c.84C>T) pathogenic?

GHSR p.Asp28= (c.84C>T) is classified Uncertain significance in GHSR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with short stature due to GHSR deficiency.

What condition is associated with GHSR p.Asp28= (c.84C>T)?

GHSR p.Asp28= (c.84C>T) is associated with short stature due to GHSR deficiency (ClinVar).

How common is GHSR p.Asp28= (c.84C>T) in the general population?

GHSR p.Asp28= (c.84C>T) is absent from gnomAD v4.1 (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.Asp28=

c.84C>T · rs748661863 · VCV901382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.7	GERP -1.5, phastCons 1
Overall
CADD	5.738	PHRED · no single calibrated threshold — expert panels disagree

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.Asp28=
Coding: c.84C>T
MANE Select: NM_198407
dbSNP: rs748661863
Type: single nucleotide variant
Location: chr3:172448330 (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

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-asp28 (accessed [today's date]).

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