Is RIPK4 p.Arg273= (c.819G>A) pathogenic?

RIPK4 p.Arg273= (c.819G>A) is classified Benign/Likely benign in RIPK4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). Rare (popmax 0.773%, afr); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Arg273= (c.819G>A)?

RIPK4 p.Arg273= (c.819G>A) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Arg273= (c.819G>A) in the general population?

RIPK4 p.Arg273= (c.819G>A) is rare (popmax 0.773%, afr) (gnomAD).

RIPK4 p.Arg273=

c.819G>A · rs139503982 · VCV340027

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.773%, afr)

Conditions

Bartsocas-Papas syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP 2.3, phastCons 1
Overall
CADD	5.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.773% African / African-American · 580/75,048 alleles

Filtering AF 0.721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.7%

Overall 0.0957% 1,541/1,609,710 alleles · rare exomes 1,116/1,457,346 · genomes 425/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.773%	129
Middle Eastern	0.382%	262
Admixed American	0.375%	266
Remaining individualsnot grpmax-eligible	0.196%	511
Ashkenazi Jewishnot grpmax-eligible	0.118%	845
European (non-Finnish)	0.0471%	2,122
South Asian	0.0011%	91,034

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.Arg273=
Coding: c.819G>A
MANE Select: NM_020639
dbSNP: rs139503982
Type: single nucleotide variant
Location: chr21:41746626 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 273: 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 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
RIPK4 p.Arg521Trp 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-arg273 (accessed [today's date]).

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