Is RIPK4 p.Arg260fs (c.777dup) pathogenic?

RIPK4 p.Arg260fs (c.777dup) is classified Pathogenic in RIPK4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-01-13). Very rare (popmax 0.000339%, nfe); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Arg260fs (c.777dup)?

RIPK4 p.Arg260fs (c.777dup) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Arg260fs (c.777dup) in the general population?

RIPK4 p.Arg260fs (c.777dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

RIPK4 p.Arg260fs

c.777dup · rs1354268287 · VCV30514

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Bartsocas-Papas syndrome 1

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.037	GERP -3.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,862 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,458,930 alleles · very rare

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: RIPK4
Protein: p.Arg260fs
Coding: c.777dup
MANE Select: NM_020639
dbSNP: rs1354268287
Type: Duplication
Location: chr21:41746667 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 260: the protein kinase domain

Full RIPK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bartsocas-Papas syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same residue
RIPK4 p.Arg260Cys Uncertain significance ★ ⚠ same residue
RIPK4 p.Arg260Ser Uncertain significance ★ ⚠ same residue
RIPK4 p.Glu359Ter Pathogenic same condition
RIPK4 c.*1361T>A Uncertain significance ★★ same condition
RIPK4 p.Ala126Val Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg241Cys Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg271Gln 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/ripk4-p-arg260fs (accessed [today's date]).

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