Is RIPK4 p.Ala645= (c.1935G>A) pathogenic?

RIPK4 p.Ala645= (c.1935G>A) is classified Likely benign in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with RIPK4 p.Ala645= (c.1935G>A)?

RIPK4 p.Ala645= (c.1935G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RIPK4 p.Ala645= (c.1935G>A) in the general population?

RIPK4 p.Ala645= (c.1935G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

RIPK4 p.Ala645=

c.1935G>A · VCV3946080

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.0018% 29/1,608,506 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,462
East Asian	0.00223%	44,864
European (non-Finnish)	0.00212%	47,179
South Asian	0.0011%	90,980

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.Ala645=
Coding: c.1935G>A
MANE Select: NM_020639
Type: single nucleotide variant
Location: chr21:41741258 (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-ala645 (accessed [today's date]).

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