Is RIPK4 p.Ser379= (c.1137C>T) pathogenic?

RIPK4 p.Ser379= (c.1137C>T) is classified Conflicting classifications of pathogenicity in RIPK4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-02). Rare (popmax 0.29%, eas); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Ser379= (c.1137C>T)?

RIPK4 p.Ser379= (c.1137C>T) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Ser379= (c.1137C>T) in the general population?

RIPK4 p.Ser379= (c.1137C>T) is rare (popmax 0.29%, eas) (gnomAD).

RIPK4 p.Ser379=

c.1137C>T · rs200420912 · VCV746355

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.29%, eas)

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 -20	GERP -3.1
Overall
CADD	0.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.29% East Asian · 130/44,856 alleles

Filtering AF 0.249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.234%

Overall 0.0098% 158/1,613,066 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.29%	345
Middle Eastern	0.0165%	6,044
Admixed American	0.00501%	19,977
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.0017%	58,991
African / African-American	0.00133%	74,996

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.Ser379=
Coding: c.1137C>T
MANE Select: NM_020639
dbSNP: rs200420912
Type: single nucleotide variant
Location: chr21:41743940 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41

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.Ser379Phe 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-ser379 (accessed [today's date]).

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