Is RIPK4 p.Ser171Phe (c.512C>T) pathogenic?

RIPK4 p.Ser171Phe (c.512C>T) is classified Uncertain significance in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: ambiguous (0.5093); Very rare (popmax 0.00381%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RIPK4 p.Ser171Phe (c.512C>T)?

RIPK4 p.Ser171Phe (c.512C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RIPK4 p.Ser171Phe (c.512C>T) in the general population?

RIPK4 p.Ser171Phe (c.512C>T) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about RIPK4 p.Ser171Phe (c.512C>T)?

AlphaMissense predicts ambiguous (score 0.5093) — an in-silico prediction, not a clinical call.

RIPK4 p.Ser171Phe

c.512C>T · rs772811394 · VCV2546092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5093	ambiguous
REVEL	0.43	indeterminate
SaProt	LLR -8.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 26 kb · p 4.3e-10 · regional, not allelic
Overall
CADD	26.7	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 0.00381% European (non-Finnish) · 45/1,180,044 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,614,128 alleles · very rare exomes 45/1,461,884 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,223
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ser171Phe
Coding: c.512C>T
MANE Select: NM_020639
dbSNP: rs772811394
Type: single nucleotide variant
Location: chr21:41751208 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.62 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.41
Residue 171: the protein kinase domain

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-ser171phe (accessed [today's date]).

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