Is RIPK4 p.Arg89= (c.267C>T) pathogenic?

RIPK4 p.Arg89= (c.267C>T) is classified Conflicting classifications of pathogenicity in RIPK4 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-01). Rare (popmax 0.423%, amr); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Arg89= (c.267C>T)?

RIPK4 p.Arg89= (c.267C>T) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Arg89= (c.267C>T) in the general population?

RIPK4 p.Arg89= (c.267C>T) is rare (popmax 0.423%, amr) (gnomAD).

RIPK4 p.Arg89=

c.267C>T · rs55798804 · VCV340035

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.423%, amr)

Conditions

Bartsocas-Papas syndrome 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 -4.2	GERP -4.8
Overall
CADD	2.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.423% Admixed American · 254/60,036 alleles

Filtering AF 0.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.364%

Overall 0.107% 1,734/1,614,232 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.423%	236
European (non-Finnish)	0.118%	849
Remaining individualsnot grpmax-eligible	0.117%	856
African / African-American	0.0147%	6,824
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,005
East Asian	0.00223%	44,884
South Asian	0.0022%	45,542

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.Arg89=
Coding: c.267C>T
MANE Select: NM_020639
dbSNP: rs55798804
Type: single nucleotide variant
Location: chr21:41756732 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 89: 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.Arg89Cys Uncertain significance ★ ⚠ same residue
RIPK4 c.*1361T>A Uncertain significance ★★ same condition
RIPK4 p.Ala126Val Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg241Cys Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg271Gln Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg320Gln Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg493Trp 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-arg89 (accessed [today's date]).

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