Is RIPK3 p.Val194Ile (c.580G>A) pathogenic?

RIPK3 p.Val194Ile (c.580G>A) is classified Likely benign in RIPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.0958); Ultra-rare (popmax 0.0869%, eas).

How common is RIPK3 p.Val194Ile (c.580G>A) in the general population?

RIPK3 p.Val194Ile (c.580G>A) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

What do computational predictors say about RIPK3 p.Val194Ile (c.580G>A)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

RIPK3 p.Val194Ile

c.580G>A · rs79855438 · VCV3154536

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.25	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 -0.18	GERP -3.1, phastCons 0.017
Regional constraint	o/e 1.01	unconstrained · MANE · 3,648 bp · p 0.89 · regional, not allelic
Overall
CADD	1.053	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0869% East Asian · 39/44,878 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00341% 55/1,613,626 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,151
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0064%	15,618
African / African-American	0.00267%	37,453
South Asian	0.0011%	91,080
European (non-Finnish)	0.000678%	147,462

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: RIPK3
Protein: p.Val194Ile
Coding: c.580G>A
MANE Select: NM_006871
dbSNP: rs79855438
Type: single nucleotide variant
Location: chr14:24338459 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.80 · 9 PDB
Residue 194: the protein kinase domain; a β-strand

Full RIPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIPK3 p.Val27Leu Uncertain significance ★★ ⚠ same type
RIPK3 p.Ala13Asp Uncertain significance ★ ⚠ same type
RIPK3 p.Ala201Thr Uncertain significance ★ ⚠ same type
RIPK3 p.Ala216Thr Uncertain significance ★ ⚠ same type
RIPK3 p.Ala56Glu Uncertain significance ★ ⚠ same type
RIPK3 p.Arg141Gln Uncertain significance ★ ⚠ same type
RIPK3 p.Arg196Trp Uncertain significance ★ ⚠ same type
RIPK3 p.Arg239Gln Uncertain significance ★ ⚠ same type

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/ripk3-p-val194ile (accessed [today's date]).

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