Is RIPK4 p.Leu766Val (c.2296C>G) pathogenic?

RIPK4 p.Leu766Val (c.2296C>G) is classified Likely benign in RIPK4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-08-22). AlphaMissense: likely benign (0.1052); Rare (popmax 0.401%, eas); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Leu766Val (c.2296C>G)?

RIPK4 p.Leu766Val (c.2296C>G) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Leu766Val (c.2296C>G) in the general population?

RIPK4 p.Leu766Val (c.2296C>G) is rare (popmax 0.401%, eas) (gnomAD).

What do computational predictors say about RIPK4 p.Leu766Val (c.2296C>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

RIPK4 p.Leu766Val

c.2296C>G · rs200025631 · VCV755418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.401%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bartsocas-Papas syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L814V vs ClinVar L766V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.401% East Asian · 180/44,868 alleles

Filtering AF 0.353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.012% 193/1,612,306 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.401%	249
Remaining individualsnot grpmax-eligible	0.0112%	8,924
South Asian	0.00549%	18,210
European (non-Finnish)	8.48e-05%	1,179,650

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.Leu766Val
Coding: c.2296C>G
MANE Select: NM_020639
dbSNP: rs200025631
Type: single nucleotide variant
Location: chr21:41740897 (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-leu766val (accessed [today's date]).

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