Is RIPK4 p.Ser379Phe (c.1136C>T) pathogenic?

RIPK4 p.Ser379Phe (c.1136C>T) is classified Uncertain significance in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely pathogenic (0.9532); Absent from gnomAD v4.1.

How common is RIPK4 p.Ser379Phe (c.1136C>T) in the general population?

RIPK4 p.Ser379Phe (c.1136C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RIPK4 p.Ser379Phe (c.1136C>T)?

AlphaMissense predicts likely pathogenic (score 0.9532) — an in-silico prediction, not a clinical call.

RIPK4 p.Ser379Phe

c.1136C>T · VCV3765857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9532	likely pathogenic
REVEL	0.503	indeterminate
SaProt	LLR -10.54	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S427F vs ClinVar S379F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RIPK4
Protein: p.Ser379Phe
Coding: c.1136C>T
MANE Select: NM_020639
Type: single nucleotide variant
Location: chr21:41743941 (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 p.Ser379= Conflicting classifications of pathogenicity ★ same residue
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

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-ser379phe (accessed [today's date]).

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