Is RIPK4 p.Val486= (c.1458C>T) pathogenic?

RIPK4 p.Val486= (c.1458C>T) is classified Likely benign in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-05). Ultra-rare (popmax 0.0133%, afr).

How common is RIPK4 p.Val486= (c.1458C>T) in the general population?

RIPK4 p.Val486= (c.1458C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

RIPK4 p.Val486=

c.1458C>T · rs773279959 · VCV730923

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

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 -6.4	GERP -4.5
Overall
CADD	0.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,924 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00186% 30/1,612,548 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,492
Remaining individualsnot grpmax-eligible	0.0032%	31,234
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,010
European (non-Finnish)	0.00127%	78,668

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.Val486=
Coding: c.1458C>T
MANE Select: NM_020639
dbSNP: rs773279959
Type: single nucleotide variant
Location: chr21:41741735 (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

Similar variants

RIPK4 c.*1361T>A Uncertain significance ★★ same type
RIPK4 p.Ala126Val Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg241Cys Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg271Gln Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg320Gln Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg493Trp Uncertain significance ★★ ⚠ same type
RIPK4 p.Arg521Trp 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/ripk4-p-val486 (accessed [today's date]).

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