Is LHCGR p.Ala7Val (c.20C>T) pathogenic?

LHCGR p.Ala7Val (c.20C>T) is classified Uncertain significance in LHCGR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.131); Very rare (popmax 0.00245%, eas); Associated with Inborn genetic diseases.

What condition is associated with LHCGR p.Ala7Val (c.20C>T)?

LHCGR p.Ala7Val (c.20C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LHCGR p.Ala7Val (c.20C>T) in the general population?

LHCGR p.Ala7Val (c.20C>T) is very rare (popmax 0.00245%, eas) (gnomAD).

What do computational predictors say about LHCGR p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.131) — an in-silico prediction, not a clinical call.

LHCGR p.Ala7Val

c.20C>T · VCV3290595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.131 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.131	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.22	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 0.23	GERP -3
Regional constraint	o/e 1.03	unconstrained · MANE · 68 kb · p 0.37 · regional, not allelic
Overall
CADD	5.781	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 0.00245% East Asian · 1/40,876 alleles

Overall 0.000145% 2/1,382,588 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00245%	40,876
South Asian	0.00119%	83,940

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: LHCGR
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_000233
Type: single nucleotide variant
Location: chr2:48755652 (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

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

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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-ala7val (accessed [today's date]).

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