Is HR p.Val804= (c.2412G>C) pathogenic?

HR p.Val804= (c.2412G>C) is classified Conflicting classifications of pathogenicity in HR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-17). Rare (popmax 0.518%, eas); Associated with atrichia with papular lesions.

What condition is associated with HR p.Val804= (c.2412G>C)?

HR p.Val804= (c.2412G>C) is associated with atrichia with papular lesions, alopecia universalis congenita (ClinVar).

How common is HR p.Val804= (c.2412G>C) in the general population?

HR p.Val804= (c.2412G>C) is rare (popmax 0.518%, eas) (gnomAD).

How is Atrichia with papular lesions inherited?

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

HR p.Val804=

c.2412G>C · rs758753031 · VCV909922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.518%, eas)

Conditions

atrichia with papular lesions

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.71 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.5	GERP -3.2
Overall
CADD	1.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.518% East Asian · 219/42,304 alleles

Filtering AF 0.462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.44%

Overall 0.0143% 224/1,565,996 alleles · rare exomes 219/1,413,802 · genomes 5/152,194 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.518%	193
Remaining individualsnot grpmax-eligible	0.00824%	12,132

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.Val804=
Coding: c.2412G>C
MANE Select: NM_005144
dbSNP: rs758753031
Type: single nucleotide variant
Location: chr8:22120914 (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-val804 (accessed [today's date]).

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