Is RIPK4 p.Thr101= (c.303G>A) pathogenic?

RIPK4 p.Thr101= (c.303G>A) is classified Benign/Likely benign in RIPK4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-04-27). Low-frequency (popmax 2.79%, eas); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Thr101= (c.303G>A)?

RIPK4 p.Thr101= (c.303G>A) is associated with Bartsocas-Papas syndrome 1, CHAND syndrome (ClinVar).

How common is RIPK4 p.Thr101= (c.303G>A) in the general population?

RIPK4 p.Thr101= (c.303G>A) is low-frequency (popmax 2.79%, eas) (gnomAD).

RIPK4 p.Thr101=

c.303G>A · rs2277792 · VCV731263

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.79%, 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 -15	GERP -5.1
Overall
CADD	1.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.79% East Asian · 1,254/44,886 alleles

Filtering AF 2.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.61%

Overall 0.131% 2,117/1,614,190 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.79%	36
Finnishnot grpmax-eligible	0.222%	451
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.15%	665
South Asian	0.0988%	1,012
Ashkenazi Jewishnot grpmax-eligible	0.0946%	1,057
European (non-Finnish)	0.0408%	2,448
African / African-American	0.012%	8,340
Admixed American	0.0117%	8,575

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.Thr101=
Coding: c.303G>A
MANE Select: NM_020639
dbSNP: rs2277792
Type: single nucleotide variant
Location: chr21:41756696 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 101: 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

Also linked: CHAND syndrome

Similar variants

RIPK4 p.Thr101Met 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-thr101 (accessed [today's date]).

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