Is GHRL p.Arg34Thr (c.101G>C) pathogenic?

GHRL p.Arg34Thr (c.101G>C) is classified Uncertain significance in GHRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1242); Very rare (popmax 0.00017%, nfe).

How common is GHRL p.Arg34Thr (c.101G>C) in the general population?

GHRL p.Arg34Thr (c.101G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about GHRL p.Arg34Thr (c.101G>C)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

GHRL p.Arg34Thr

c.101G>C · rs2470359545 · VCV3099741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.5, phastCons 0.86
Regional constraint	o/e 1.36	unconstrained · MANE · 4,302 bp · p 2e-05 · regional, not allelic
Overall
CADD	16.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,442 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,150 alleles · very rare exomes 2/1,459,876 · genomes 0/152,274 · joint denominator

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: GHRL
Protein: p.Arg34Thr
Coding: c.101G>C
MANE Select: NM_016362
dbSNP: rs2470359545
Type: single nucleotide variant
Location: chr3:10290080 (GRCh38)
Gene constraint: LOEUF 1.822 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.12 · 4 PDB
Residue 34: an α-helix; the 'disordered' region

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

Similar variants

GHRL c.109-36G>A Benign ★★ same type
GHRL c.226-286C>T Benign ★★ same type
GHRL c.226-313A>G Benign ★★ same type
GHRL c.334+138T>G Benign ★★ same type
GHRL p.Gln90Leu Benign ★★ same type
GHRL c.225+2T>G Uncertain significance ★ same type
GHRL c.-771G>A Uncertain significance ★ same type
GHRL c.-789C>T Uncertain significance ★ 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/ghrl-p-arg34thr (accessed [today's date]).

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