Is HR p.Pro1113= (c.3339C>A) pathogenic?

HR p.Pro1113= (c.3339C>A) is classified Benign/Likely benign in HR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Common (popmax 9.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with atrichia with papular lesions.

What condition is associated with HR p.Pro1113= (c.3339C>A)?

HR p.Pro1113= (c.3339C>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.Pro1113=

Q: How common is HR p.Pro1113= (c.3339C>A) in the general population?

HR p.Pro1113= (c.3339C>A) is common (popmax 9.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3339C>A · rs112173147 · VCV362477

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.3%, mid) — 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 -8.9	GERP -3.5
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.3% Middle Eastern · 412/4,428 alleles

Filtering AF 8.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.63%

Overall 7.68% 119,718/1,559,404 alleles · common exomes 111,114/1,407,118 · genomes 8,604/152,286 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	14.2%	7
Middle Easterngrpmax	9.3%	11
European (non-Finnish)	8.7%	11
South Asian	8.11%	12
Remaining individualsnot grpmax-eligible	7.05%	14
Finnishnot grpmax-eligible	5.45%	18
Admixed American	4.22%	24
Ashkenazi Jewishnot grpmax-eligible	3.82%	26
African / African-American	1.52%	66
East Asian	0.0421%	2,376

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1113=
Coding: c.3339C>A
MANE Select: NM_005144
dbSNP: rs112173147
Type: single nucleotide variant
Location: chr8:22116914 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 1113: the jmjc domain

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.Pro1113His Uncertain significance ★ ⚠ same residue
HR p.Pro1113Ser Uncertain significance ★ ⚠ 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

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-pro1113 (accessed [today's date]).

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