Is GH1 p.Asp156= (c.468T>C) pathogenic?

GH1 p.Asp156= (c.468T>C) is classified Conflicting classifications of pathogenicity in GH1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-09). Ultra-rare (popmax 0.0312%, eas); Associated with Decreased response to growth hormone stimulation test.

What condition is associated with GH1 p.Asp156= (c.468T>C)?

GH1 p.Asp156= (c.468T>C) is associated with Decreased response to growth hormone stimulation test (ClinVar).

How common is GH1 p.Asp156= (c.468T>C) in the general population?

GH1 p.Asp156= (c.468T>C) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

GH1 p.Asp156=

c.468T>C · rs201849388 · VCV891325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Conditions

Decreased response to growth hormone stimulation test

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 -9.1	GERP -3.4
Overall
CADD	0.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,876 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0154% 248/1,613,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
Remaining individualsnot grpmax-eligible	0.0352%	2,841
East Asiangrpmax	0.0312%	3,205
Admixed American	0.03%	3,334
Middle Eastern	0.0165%	6,056
South Asian	0.011%	9,108
European (non-Finnish)	0.0107%	9,364
Finnishnot grpmax-eligible	0.00937%	10,672
African / African-American	0.00133%	75,032

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GH1
Protein: p.Asp156=
Coding: c.468T>C
MANE Select: NM_000515
dbSNP: rs201849388
Type: single nucleotide variant
Location: chr17:63917495 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 10 PDB
Residue 156: a disulfide bond

Full GH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Decreased response to growth hormone stimulation test — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GH1 p.Glu82Asp Uncertain significance ★★ ⚠ same condition
GH1 c.-38A>C Benign/Likely benign ★★ same condition
GH1 c.-4T>G Benign/Likely benign ★★ same condition
GH1 c.292-15G>A Uncertain significance ★ same condition
GH1 p.Ala50= Conflicting classifications of pathogenicity ★ same condition
GH1 p.Val136Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
GH1 c.291+1G>A Pathogenic ★★ same type
GH1 c.291+5G>A Pathogenic ★★ same type

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/gh1-p-asp156 (accessed [today's date]).

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