Is GHSR p.Pro177= (c.531C>A) pathogenic?

GHSR p.Pro177= (c.531C>A) is classified Benign/Likely benign in GHSR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.52%, nfe); Associated with short stature due to GHSR deficiency.

What condition is associated with GHSR p.Pro177= (c.531C>A)?

GHSR p.Pro177= (c.531C>A) is associated with short stature due to GHSR deficiency (ClinVar).

How common is GHSR p.Pro177= (c.531C>A) in the general population?

GHSR p.Pro177= (c.531C>A) is rare (popmax 0.52%, nfe) (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.Pro177=

c.531C>A · rs4988509 · VCV698005

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.52%, nfe)

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 6	GERP 0.06, phastCons 1
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.52% European (non-Finnish) · 6,134/1,179,492 alleles

Filtering AF 0.509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.505%

Overall 0.426% 6,872/1,613,452 alleles · rare exomes 6,395/1,461,116 · genomes 477/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.52%	192
Finnishnot grpmax-eligible	0.488%	205
Remaining individualsnot grpmax-eligible	0.37%	270
Admixed American	0.105%	953
Middle Eastern	0.099%	1,010
African / African-American	0.0666%	1,501
South Asian	0.0648%	1,544
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,850
East Asian	0.00223%	44,858

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.Pro177=
Coding: c.531C>A
MANE Select: NM_198407
dbSNP: rs4988509
Type: single nucleotide variant
Location: chr3:172447883 (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.Pro177Ser Uncertain significance ★ ⚠ same residue
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

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-pro177 (accessed [today's date]).

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