Is RNASEL p.Phe420= (c.1260C>T) pathogenic?

RNASEL p.Phe420= (c.1260C>T) is classified Uncertain significance in RNASEL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-08-17). Ultra-rare (popmax 0.0801%, sas); Associated with prostate cancer, hereditary, 1.

What condition is associated with RNASEL p.Phe420= (c.1260C>T)?

RNASEL p.Phe420= (c.1260C>T) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is RNASEL p.Phe420= (c.1260C>T) in the general population?

RNASEL p.Phe420= (c.1260C>T) is ultra-rare (popmax 0.0801%, sas) (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

RNASEL p.Phe420=

c.1260C>T · rs540408368 · VCV1702926

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0801%, sas)

Conditions

prostate cancer, hereditary, 1

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 3.2	GERP 0.65, phastCons 1
Overall
CADD	10.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0801% South Asian · 73/91,086 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.00465% 75/1,614,140 alleles · ultra-rare exomes 70/1,461,890 · genomes 5/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0801%	1,248
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,030

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: RNASEL
Protein: p.Phe420=
Coding: c.1260C>T
MANE Select: NM_021133
dbSNP: rs540408368
Type: single nucleotide variant
Location: chr1:182585547 (GRCh38)
Gene constraint: LOEUF 0.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.96 · 5 PDB
Residue 420: the protein kinase domain; a UniProt-annotated variant site (found in a patient with multisystem inflammatory syndrome; uncertain significance); a β-strand

Full RNASEL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

RNASEL p.Phe420fs Uncertain significance same residue
RNASEL p.Phe420Ile Uncertain significance ★ ⚠ same residue
RNASEL c.1481-1G>T Uncertain significance ★ same condition
RNASEL p.Ala176Thr Uncertain significance ★ ⚠ same condition
RNASEL p.Gln619Ter Uncertain significance ★ same condition
RNASEL p.Gln693Glu Uncertain significance ★ ⚠ same condition
RNASEL p.Glu265Ter Conflicting classifications of pathogenicity ★ same condition
RNASEL p.Val531Met 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/rnasel-p-phe420 (accessed [today's date]).

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