Is RIPK1 p.Arg413= (c.1239C>T) pathogenic?

RIPK1 p.Arg413= (c.1239C>T) is classified Likely benign in RIPK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0165%, mid).

How common is RIPK1 p.Arg413= (c.1239C>T) in the general population?

RIPK1 p.Arg413= (c.1239C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RIPK1 p.Arg413=

c.1239C>T · rs772082463 · VCV1982609

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.041	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -4.5, phastCons 0.008
Overall
CADD	5.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00198% 32/1,614,148 alleles · ultra-rare exomes 32/1,461,800 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00799%	12,510
Remaining individualsnot grpmax-eligible	0.0048%	20,836
South Asian	0.0022%	45,541
European (non-Finnish)	0.00169%	58,999

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: RIPK1
Protein: p.Arg413=
Coding: c.1239C>T
MANE Select: NM_001354930
dbSNP: rs772082463
Type: single nucleotide variant
Location: chr6:3105714 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.38 · 39 PDB
Residue 413: the 'interaction with sqstm1' region; the 'disordered' region

Full RIPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIPK1 p.Arg413Cys Uncertain significance ★★ ⚠ same residue
RIPK1 p.Arg413His Conflicting classifications of pathogenicity ★ ⚠ same residue
RIPK1 p.Asp324Asn Pathogenic ★★ ⚠ same type
RIPK1 p.Asp324His Pathogenic ★★ ⚠ same type
RIPK1 c.460-5C>A Uncertain significance ★★ same type
RIPK1 p.Ala106Val Uncertain significance ★★ ⚠ same type
RIPK1 p.Ala160Thr Uncertain significance ★★ ⚠ same type
RIPK1 p.Ala194Thr Uncertain significance ★★ ⚠ same type

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/ripk1-p-arg413 (accessed [today's date]).

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