Is RIPK4 p.Arg780Gln (c.2339G>A) pathogenic?

RIPK4 p.Arg780Gln (c.2339G>A) is classified Likely benign in RIPK4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-05). AlphaMissense: likely benign (0.0747); Rare (popmax 0.27%, afr); Associated with Inborn genetic diseases.

What condition is associated with RIPK4 p.Arg780Gln (c.2339G>A)?

RIPK4 p.Arg780Gln (c.2339G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RIPK4 p.Arg780Gln (c.2339G>A) in the general population?

RIPK4 p.Arg780Gln (c.2339G>A) is rare (popmax 0.27%, afr) (gnomAD).

What do computational predictors say about RIPK4 p.Arg780Gln (c.2339G>A)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

RIPK4 p.Arg780Gln

c.2339G>A · rs147337665 · VCV3049637

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.27%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.59	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 0.5	GERP -3.5, phastCons 0.07
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	6.843	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 R828Q vs ClinVar R780Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.27% African / African-American · 202/74,946 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.227%

Overall 0.0173% 278/1,607,128 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.27%	371
Admixed American	0.0368%	2,714
Middle Eastern	0.0348%	2,870
Remaining individualsnot grpmax-eligible	0.0145%	6,915
European (non-Finnish)	0.0034%	29,431
East Asian	0.00223%	44,776
South Asian	0.00221%	45,255

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.Arg780Gln
Coding: c.2339G>A
MANE Select: NM_020639
dbSNP: rs147337665
Type: single nucleotide variant
Location: chr21:41740854 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIPK4 p.Arg780Trp Uncertain significance ★ ⚠ same residue
RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg320Gln Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg538Trp Uncertain significance ★★ ⚠ same condition
RIPK4 p.Gly485Ser Uncertain significance ★★ ⚠ same condition
RIPK4 p.Leu778Phe Uncertain significance ★★ ⚠ same condition
RIPK4 p.Thr101Met Uncertain significance ★★ ⚠ same condition
RIPK4 p.Val247Met 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-arg780gln (accessed [today's date]).

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