Is RIPK4 p.Ser437= (c.1311C>T) pathogenic?

RIPK4 p.Ser437= (c.1311C>T) is classified Benign/Likely benign in RIPK4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-03-23). Low-frequency (popmax 3.44%, afr); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Ser437= (c.1311C>T)?

RIPK4 p.Ser437= (c.1311C>T) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Ser437= (c.1311C>T) in the general population?

RIPK4 p.Ser437= (c.1311C>T) is low-frequency (popmax 3.44%, afr) (gnomAD).

RIPK4 p.Ser437=

c.1311C>T · rs56149248 · VCV340021

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.44%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -2.4
Overall
CADD	6.927	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.44% African / African-American · 2,582/75,032 alleles

Filtering AF 3.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.29%

Overall 0.2% 3,220/1,613,402 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.44%	29
Admixed American	0.346%	289
Remaining individualsnot grpmax-eligible	0.29%	345
Middle Eastern	0.198%	505
South Asian	0.0505%	1,980
European (non-Finnish)	0.016%	6,243
East Asian	0.00446%	22,436

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.Ser437=
Coding: c.1311C>T
MANE Select: NM_020639
dbSNP: rs56149248
Type: single nucleotide variant
Location: chr21:41741882 (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 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-ser437 (accessed [today's date]).

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