Is GHSR p.Arg70= (c.210C>T) pathogenic?

GHSR p.Arg70= (c.210C>T) is classified Benign/Likely benign in GHSR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-29). Rare (popmax 0.633%, sas); Associated with short stature due to GHSR deficiency.

What condition is associated with GHSR p.Arg70= (c.210C>T)?

GHSR p.Arg70= (c.210C>T) is associated with short stature due to GHSR deficiency (ClinVar).

How common is GHSR p.Arg70= (c.210C>T) in the general population?

GHSR p.Arg70= (c.210C>T) is rare (popmax 0.633%, sas) (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.Arg70=

c.210C>T · rs200978184 · VCV901379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.633%, sas)

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 1.7	GERP 1.9, phastCons 1
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.633% South Asian · 577/91,090 alleles

Filtering AF 0.591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.574%

Overall 0.0381% 615/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.633%	158
Remaining individualsnot grpmax-eligible	0.032%	3,125
European (non-Finnish)	0.00144%	69,415
African / African-American	0.00133%	75,080

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.Arg70=
Coding: c.210C>T
MANE Select: NM_198407
dbSNP: rs200978184
Type: single nucleotide variant
Location: chr3:172448204 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB
Residue 70: 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.Arg70Leu Uncertain significance ★ ⚠ same residue
GHSR p.Arg70Pro 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

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-arg70 (accessed [today's date]).

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