Is LHCGR p.Val596fs (c.1786del) pathogenic?

LHCGR p.Val596fs (c.1786del) is classified Likely pathogenic in LHCGR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). Associated with familial male-limited precocious puberty.

What condition is associated with LHCGR p.Val596fs (c.1786del)?

LHCGR p.Val596fs (c.1786del) is associated with familial male-limited precocious puberty, Leydig cell hypoplasia, type 1 (ClinVar).

LHCGR p.Val596fs

Q: How is Familial peripheral male-limited precocious puberty inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1786del · VCV3586722

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial male-limited precocious puberty

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	GERP -0.23, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: LHCGR
Protein: p.Val596fs
Coding: c.1786del
MANE Select: NM_000233
Type: Deletion
Location: chr2:48688011 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.95 · 4 PDB

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

Disease context

familial male-limited precocious puberty — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leydig cell hypoplasia, type 1

For Familial peripheral male-limited precocious puberty (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: <1 / 1 000 000 (Europe)

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LHCGR p.Asp564Gly Pathogenic ★★ same condition
LHCGR p.Asp578Gly Pathogenic ★★ ⚠ same condition
LHCGR p.Ile542Leu Pathogenic ★★ ⚠ same condition
LHCGR p.Thr577Ile Pathogenic/Likely pathogenic ★★ 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/lhcgr-p-val596fs (accessed [today's date]).

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