Is GHSR p.Val68Ala (c.203T>C) pathogenic?

GHSR p.Val68Ala (c.203T>C) is classified Uncertain significance in GHSR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely pathogenic (0.8069); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with GHSR p.Val68Ala (c.203T>C)?

GHSR p.Val68Ala (c.203T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GHSR p.Val68Ala (c.203T>C) in the general population?

GHSR p.Val68Ala (c.203T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about GHSR p.Val68Ala (c.203T>C)?

AlphaMissense predicts likely pathogenic (score 0.8069) — an in-silico prediction, not a clinical call.

GHSR p.Val68Ala

c.203T>C · VCV3520110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8069	likely pathogenic
REVEL	0.726	pathogenic-leaning
SaProt	LLR -9.22	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,249 bp · p 0.34 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 0.000124% 2/1,614,020 alleles · very rare exomes 1/1,461,780 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Val68Ala
Coding: c.203T>C
MANE Select: NM_198407
Type: single nucleotide variant
Location: chr3:172448211 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB
Residue 68: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GHSR p.Val68= Likely benign ★★ same residue
GHSR p.Arg141Pro Uncertain significance ★★ ⚠ same condition
GHSR p.Ile58Met Uncertain significance ★★ ⚠ same condition
GHSR p.Leu274Phe Uncertain significance ★★ ⚠ same condition
GHSR p.Phe220Cys Uncertain significance ★★ ⚠ same condition
GHSR p.Thr229Met Uncertain significance ★★ ⚠ same condition
GHSR p.Thr49Ile Uncertain significance ★★ ⚠ same condition
GHSR p.Thr64Ser 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-val68ala (accessed [today's date]).

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