Is RIPK4 p.Thr647= (c.1941G>A) pathogenic?

RIPK4 p.Thr647= (c.1941G>A) is classified Benign/Likely benign in RIPK4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-22). Low-frequency (popmax 1.05%, afr); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Thr647= (c.1941G>A)?

RIPK4 p.Thr647= (c.1941G>A) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Thr647= (c.1941G>A) in the general population?

RIPK4 p.Thr647= (c.1941G>A) is low-frequency (popmax 1.05%, afr) (gnomAD).

RIPK4 p.Thr647=

c.1941G>A · rs116160025 · VCV340016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, afr)

Conditions

Bartsocas-Papas syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -4.5
Overall
CADD	1.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.05% African / African-American · 791/75,034 alleles

Filtering AF 0.993% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.969%

Overall 0.0556% 895/1,608,690 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.05%	95
Remaining individualsnot grpmax-eligible	0.0753%	1,328
Admixed American	0.05%	1,998
Middle Eastern	0.0165%	6,056
South Asian	0.0044%	22,737
European (non-Finnish)	0.00187%	53,603

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.Thr647=
Coding: c.1941G>A
MANE Select: NM_020639
dbSNP: rs116160025
Type: single nucleotide variant
Location: chr21:41741252 (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-thr647 (accessed [today's date]).

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