Is RIPK4 p.Val479Met (c.1435G>A) pathogenic?

RIPK4 p.Val479Met (c.1435G>A) is classified Uncertain significance in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: ambiguous (0.4481); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with RIPK4 p.Val479Met (c.1435G>A)?

RIPK4 p.Val479Met (c.1435G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RIPK4 p.Val479Met (c.1435G>A) in the general population?

RIPK4 p.Val479Met (c.1435G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about RIPK4 p.Val479Met (c.1435G>A)?

AlphaMissense predicts ambiguous (score 0.4481) — an in-silico prediction, not a clinical call.

RIPK4 p.Val479Met

c.1435G>A · VCV3946073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4481	ambiguous
REVEL	0.359	indeterminate
SaProt	LLR -12.93	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	23.9	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 V527M vs ClinVar V479M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000993% 16/1,611,850 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
African / African-American	0.004%	24,985
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000763%	131,115

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.Val479Met
Coding: c.1435G>A
MANE Select: NM_020639
Type: single nucleotide variant
Location: chr21:41741758 (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.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
RIPK4 p.Val347Ile 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-val479met (accessed [today's date]).

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