Is HR p.Gln528= (c.1584G>A) pathogenic?

HR p.Gln528= (c.1584G>A) is classified Uncertain significance in HR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with atrichia with papular lesions.

What condition is associated with HR p.Gln528= (c.1584G>A)?

HR p.Gln528= (c.1584G>A) is associated with atrichia with papular lesions, alopecia universalis congenita (ClinVar).

How common is HR p.Gln528= (c.1584G>A) in the general population?

HR p.Gln528= (c.1584G>A) is absent from gnomAD v4.1 (gnomAD).

How is Atrichia with papular lesions inherited?

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

HR p.Gln528=

c.1584G>A · rs1826862480 · VCV908091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

atrichia with papular lesions

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 -0.4	GERP -3.1
Overall
CADD	0.559	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: HR
Protein: p.Gln528=
Coding: c.1584G>A
MANE Select: NM_005144
dbSNP: rs1826862480
Type: single nucleotide variant
Location: chr8:22125477 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 528: the 'disordered' region

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

Disease context

atrichia with papular lesions — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: alopecia universalis congenita

For Atrichia with papular lesions (Orphanet):

Inheritance: Autosomal recessive

Similar variants

HR p.Gln528Arg Benign ★★ same residue
HR p.Arg940Ter Pathogenic ★★ same condition
HR c.*180G>A Uncertain significance ★★ same condition
HR c.*295G>A Uncertain significance ★★ same condition
HR p.Arg1099Leu Uncertain significance ★★ ⚠ same condition
HR p.Arg518Trp Uncertain significance ★★ ⚠ same condition
HR p.Arg856Gly Uncertain significance ★★ ⚠ same condition
HR p.Arg998Gln 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/hr-p-gln528 (accessed [today's date]).

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