Is RIPK4 p.Thr283= (c.849C>T) pathogenic?

RIPK4 p.Thr283= (c.849C>T) is classified Likely benign in RIPK4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-20). Ultra-rare (popmax 0.0164%, mid); Associated with RIPK4-related disorder.

What condition is associated with RIPK4 p.Thr283= (c.849C>T)?

RIPK4 p.Thr283= (c.849C>T) is associated with RIPK4-related disorder (ClinVar).

How common is RIPK4 p.Thr283= (c.849C>T) in the general population?

RIPK4 p.Thr283= (c.849C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

RIPK4 p.Thr283=

c.849C>T · rs1356031463 · VCV3051172

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

RIPK4-related disorder

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 -15	GERP -3.7
Overall
CADD	0.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000868% 14/1,613,796 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00439%	22,763
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00312%	32,013
African / African-American	0.00133%	74,926
European (non-Finnish)	0.000339%	294,955

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.Thr283=
Coding: c.849C>T
MANE Select: NM_020639
dbSNP: rs1356031463
Type: single nucleotide variant
Location: chr21:41745846 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 283: the protein kinase domain

Full RIPK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RIPK4-related disorder

Similar variants

RIPK4 p.Thr283Ser Uncertain significance ★ ⚠ same residue
RIPK4 p.Val272Leu Uncertain significance ★ ⚠ same condition
RIPK4 p.Ala611= Likely benign same condition
RIPK4 p.Arg614= Likely benign same condition
RIPK4 p.Gln769= Likely benign same condition
RIPK4 p.His240= Likely benign same condition
RIPK4 p.His547= Likely benign same condition
RIPK4 p.Ile414= Likely benign 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-thr283 (accessed [today's date]).

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