Is HR p.Asp790= (c.2370T>C) pathogenic?

HR p.Asp790= (c.2370T>C) is classified Benign in HR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 32.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with alopecia universalis congenita.

What condition is associated with HR p.Asp790= (c.2370T>C)?

HR p.Asp790= (c.2370T>C) is associated with alopecia universalis congenita, atrichia with papular lesions (ClinVar).

How is Alopecia universalis inherited?

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

HR p.Asp790=

Q: How common is HR p.Asp790= (c.2370T>C) in the general population?

HR p.Asp790= (c.2370T>C) is common (popmax 32.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2370T>C · rs57903149 · VCV362495

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 32.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

alopecia universalis congenita

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 · A>T here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.9	GERP -2.9
Overall
CADD	0.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.9% African / African-American · 24,557/74,712 alleles

Filtering AF 32.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.4%

Overall 3.59% 57,345/1,597,588 alleles · common exomes 40,797/1,445,448 · genomes 16,548/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	32.9%	3
Ashkenazi Jewishnot grpmax-eligible	7.92%	13
Middle Eastern	7.18%	14
Remaining individualsnot grpmax-eligible	5.1%	20
Admixed American	4.31%	23
South Asian	3.17%	32
Finnishnot grpmax-eligible	2.17%	46
European (non-Finnish)	1.68%	59
East Asian	1.2%	83
Amishnot grpmax-eligible	0.219%	456

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.Asp790=
Coding: c.2370T>C
MANE Select: NM_005144
dbSNP: rs57903149
Type: single nucleotide variant
Location: chr8:22120956 (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

alopecia universalis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atrichia with papular lesions

For Alopecia universalis (Orphanet):

Inheritance: Autosomal recessive, Multigenic/multifactorial
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

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-asp790 (accessed [today's date]).

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