Is HR p.Lys9= (c.27G>A) pathogenic?

HR p.Lys9= (c.27G>A) is classified Benign in HR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Common (popmax 9.47%, afr) — too common for a highly-penetrant pathogenic allele; Associated with atrichia with papular lesions.

What condition is associated with HR p.Lys9= (c.27G>A)?

HR p.Lys9= (c.27G>A) is associated with atrichia with papular lesions, alopecia universalis congenita (ClinVar).

How is Atrichia with papular lesions inherited?

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

HR p.Lys9=

Q: How common is HR p.Lys9= (c.27G>A) in the general population?

HR p.Lys9= (c.27G>A) is common (popmax 9.47%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.27G>A · rs77620102 · VCV362534

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 9.47%, afr) — too common for a highly-penetrant pathogenic allele

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 2.6	GERP 0.29, phastCons 1
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.47% African / African-American · 6,875/72,604 alleles

Filtering AF 9.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.21%

Overall 0.571% 8,840/1,548,222 alleles · common exomes 4,581/1,395,900 · genomes 4,259/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.47%	11
East Asian	0.901%	111
Remaining individualsnot grpmax-eligible	0.732%	137
Admixed American	0.704%	142
Middle Eastern	0.612%	163
Finnishnot grpmax-eligible	0.416%	241
South Asian	0.107%	932
European (non-Finnish)	0.0354%	2,823

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: HR
Protein: p.Lys9=
Coding: c.27G>A
MANE Select: NM_005144
dbSNP: rs77620102
Type: single nucleotide variant
Location: chr8:22129144 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 9: 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.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
HR p.Glu985Lys 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-lys9 (accessed [today's date]).

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