Is RIPK4 p.Ser53= (c.159G>A) pathogenic?

RIPK4 p.Ser53= (c.159G>A) is classified Benign in RIPK4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-11-02). Common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Ser53= (c.159G>A)?

RIPK4 p.Ser53= (c.159G>A) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

RIPK4 p.Ser53=

Q: How common is RIPK4 p.Ser53= (c.159G>A) in the general population?

RIPK4 p.Ser53= (c.159G>A) is common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.159G>A · rs6586238 · VCV340036

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 18.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.47	GERP -2.3, phastCons 0.049
Overall
CADD	14.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% African / African-American · 13,737/74,472 alleles

Filtering AF 18.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.1%

Overall 13.7% 220,038/1,609,716 alleles · common exomes 199,172/1,457,676 · genomes 20,866/152,040 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.4%	5
European (non-Finnish)	15.2%	7
Remaining individualsnot grpmax-eligible	12.5%	8
Finnishnot grpmax-eligible	12.1%	8
Middle Eastern	7.95%	13
Admixed American	7.19%	14
Amishnot grpmax-eligible	6.81%	15
Ashkenazi Jewishnot grpmax-eligible	6.46%	15
South Asian	6.03%	17
East Asian	0.0224%	4,456

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.Ser53=
Coding: c.159G>A
MANE Select: NM_020639
dbSNP: rs6586238
Type: single nucleotide variant
Location: chr21:41766883 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 53: 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-ser53 (accessed [today's date]).

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