Is RIPK1 p.Pro276= (c.828G>A) pathogenic?

RIPK1 p.Pro276= (c.828G>A) is classified Likely benign in RIPK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-15). Very rare (popmax 0.00549%, sas).

How common is RIPK1 p.Pro276= (c.828G>A) in the general population?

RIPK1 p.Pro276= (c.828G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

RIPK1 p.Pro276=

c.828G>A · rs774820485 · VCV1573930

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -0.48	GERP -5
Overall
CADD	7.507	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,074 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00242% 39/1,614,026 alleles · very rare exomes 34/1,461,830 · genomes 5/152,196 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00246%	40,690
Admixed American	0.00167%	60,004

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.Pro276=
Coding: c.828G>A
MANE Select: NM_001354930
dbSNP: rs774820485
Type: single nucleotide variant
Location: chr6:3085398 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.38 · 39 PDB
Residue 276: the protein kinase domain

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

Similar variants

RIPK1 p.Pro276Arg Uncertain significance ★ ⚠ same residue
RIPK1 p.Pro276Leu Uncertain significance ★ ⚠ 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-pro276 (accessed [today's date]).

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