Is HR p.Pro716fs (c.2147del) pathogenic?

HR p.Pro716fs (c.2147del) is classified Pathogenic in HR (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-21). No gnomAD frequency available for this variant; Associated with atrichia with papular lesions.

What condition is associated with HR p.Pro716fs (c.2147del)?

HR p.Pro716fs (c.2147del) is associated with atrichia with papular lesions (ClinVar).

How common is HR p.Pro716fs (c.2147del) in the general population?

HR p.Pro716fs (c.2147del) is no gnomAD frequency available for this variant (gnomAD).

How is Atrichia with papular lesions inherited?

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

HR p.Pro716fs

c.2147del · rs2131756993 · VCV1075245

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

atrichia with papular lesions

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.23	GERP -0.48

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HR
Protein: p.Pro716fs
Coding: c.2147del
MANE Select: NM_005144
dbSNP: rs2131756993
Type: Deletion
Location: chr8:22121669 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 716: 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

For Atrichia with papular lesions (Orphanet):

Inheritance: Autosomal recessive

Similar variants

HR p.Arg1067fs Likely pathogenic ★ same condition
HR p.Gln663fs Likely pathogenic ★ same condition
HR c.2847-2_2847-1del Pathogenic same condition
HR p.Gln420fs Pathogenic same condition
HR p.Arg940Ter Pathogenic ★★ same condition
HR p.Ser667fs Pathogenic ★★ same condition
HR c.*180G>A Uncertain significance ★★ same condition
HR c.*295G>A 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-pro716fs (accessed [today's date]).

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