Is ANOS1 p.Lys124= (c.372A>G) pathogenic?

ANOS1 p.Lys124= (c.372A>G) is classified Uncertain significance in ANOS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). Absent from gnomAD v4.1; Associated with hypogonadotropic hypogonadism 1 with or without anosmia.

What condition is associated with ANOS1 p.Lys124= (c.372A>G)?

ANOS1 p.Lys124= (c.372A>G) is associated with hypogonadotropic hypogonadism 1 with or without anosmia (ClinVar).

How common is ANOS1 p.Lys124= (c.372A>G) in the general population?

ANOS1 p.Lys124= (c.372A>G) is absent from gnomAD v4.1 (gnomAD).

ANOS1 p.Lys124=

c.372A>G · VCV3598482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypogonadotropic hypogonadism 1 with or without anosmia

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 0.08	GERP 1.9, phastCons 0.012
Overall
CADD	5.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANOS1
Protein: p.Lys124=
Coding: c.372A>G
MANE Select: NM_000216
Type: single nucleotide variant
Location: chrX:8597203 (GRCh38)
Structure: AlphaFold pLDDT 76.88 · 1 PDB

Full ANOS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypogonadotropic hypogonadism 1 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANOS1 c.1063-1G>C Pathogenic/Likely pathogenic ★★ same condition
ANOS1 c.1449+1G>A Pathogenic/Likely pathogenic ★★ same condition
ANOS1 p.Arg247Ter Pathogenic/Likely pathogenic ★★ same condition
ANOS1 p.Arg262Ter Pathogenic ★★ same condition
ANOS1 p.Arg272Ter Pathogenic ★★ same condition
ANOS1 p.Arg423Ter Pathogenic ★★ same condition
ANOS1 p.Arg424Ter Pathogenic ★★ same condition
ANOS1 p.Arg457Ter 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/anos1-p-lys124 (accessed [today's date]).

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