Is HR p.Cys487= (c.1461C>T) pathogenic?

HR p.Cys487= (c.1461C>T) is classified Benign in HR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). Low-frequency (popmax 3.65%, afr); Associated with atrichia with papular lesions.

What condition is associated with HR p.Cys487= (c.1461C>T)?

HR p.Cys487= (c.1461C>T) is associated with atrichia with papular lesions, alopecia universalis congenita (ClinVar).

How common is HR p.Cys487= (c.1461C>T) in the general population?

HR p.Cys487= (c.1461C>T) is low-frequency (popmax 3.65%, afr) (gnomAD).

How is Atrichia with papular lesions inherited?

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

HR p.Cys487=

c.1461C>T · rs78703240 · VCV362517

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.65%, afr)

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 0.62	GERP -0.84, phastCons 0.026
Overall
CADD	1.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.65% African / African-American · 2,740/75,050 alleles

Filtering AF 3.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.49%

Overall 0.186% 2,995/1,613,880 alleles · low-frequency exomes 1,395/1,461,520 · genomes 1,600/152,360 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.65%	27
Remaining individualsnot grpmax-eligible	0.206%	484
Admixed American	0.16%	625
Middle Eastern	0.0663%	1,509
South Asian	0.0044%	22,744
European (non-Finnish)	0.00186%	53,635

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.Cys487=
Coding: c.1461C>T
MANE Select: NM_005144
dbSNP: rs78703240
Type: single nucleotide variant
Location: chr8:22125677 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65

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-cys487 (accessed [today's date]).

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