Is RIPK4 p.Ala577Gly (c.1730C>G) pathogenic?

RIPK4 p.Ala577Gly (c.1730C>G) is classified Uncertain significance in RIPK4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). AlphaMissense: ambiguous (0.3939); Absent from gnomAD v4.1.

How common is RIPK4 p.Ala577Gly (c.1730C>G) in the general population?

RIPK4 p.Ala577Gly (c.1730C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RIPK4 p.Ala577Gly (c.1730C>G)?

AlphaMissense predicts ambiguous (score 0.3939) — an in-silico prediction, not a clinical call.

RIPK4 p.Ala577Gly

c.1730C>G · rs1569098803 · VCV591590

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3939 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3939	ambiguous
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -8.47	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	24.3	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 A625G vs ClinVar A577G) — 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.Ala577Gly
Coding: c.1730C>G
MANE Select: NM_020639
dbSNP: rs1569098803
Type: single nucleotide variant
Location: chr21:41741463 (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.Ala577Thr Uncertain significance ★ ⚠ 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-ala577gly (accessed [today's date]).

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