Is RIPK4 p.Ala775= (c.2325C>T) pathogenic?

RIPK4 p.Ala775= (c.2325C>T) is classified Benign/Likely benign in RIPK4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-29). Rare (popmax 0.373%, eas); Associated with Bartsocas-Papas syndrome 1.

What condition is associated with RIPK4 p.Ala775= (c.2325C>T)?

RIPK4 p.Ala775= (c.2325C>T) is associated with Bartsocas-Papas syndrome 1 (ClinVar).

How common is RIPK4 p.Ala775= (c.2325C>T) in the general population?

RIPK4 p.Ala775= (c.2325C>T) is rare (popmax 0.373%, eas) (gnomAD).

RIPK4 p.Ala775=

c.2325C>T · rs148947402 · VCV340010

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.373%, eas)

Conditions

Bartsocas-Papas syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	0.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.373% East Asian · 167/44,820 alleles

Filtering AF 0.326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.0119% 192/1,610,120 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.373%	268
Remaining individualsnot grpmax-eligible	0.00962%	10,392
African / African-American	0.00267%	37,502
Admixed American	0.00167%	59,854
European (non-Finnish)	0.00127%	78,579
South Asian	0.0011%	90,886

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.Ala775=
Coding: c.2325C>T
MANE Select: NM_020639
dbSNP: rs148947402
Type: single nucleotide variant
Location: chr21:41740868 (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

Bartsocas-Papas syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIPK4 p.Ala775Thr Benign/Likely benign ★★ same residue
RIPK4 c.*1361T>A Uncertain significance ★★ same condition
RIPK4 p.Ala126Val Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg241Cys Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg260His Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg271Gln Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg320Gln Uncertain significance ★★ ⚠ same condition
RIPK4 p.Arg493Trp 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-ala775 (accessed [today's date]).

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