Is RIPK4 p.His642= (c.1926C>T) pathogenic?

RIPK4 p.His642= (c.1926C>T) is classified Likely benign in RIPK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-01). Ultra-rare (popmax 0.0822%, mid).

How common is RIPK4 p.His642= (c.1926C>T) in the general population?

RIPK4 p.His642= (c.1926C>T) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

RIPK4 p.His642=

c.1926C>T · rs201057277 · VCV744263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.065	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -4.5
Overall
CADD	6.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,082 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.0207% 333/1,608,352 alleles · ultra-rare exomes 311/1,456,096 · genomes 22/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,216
Admixed American	0.05%	1,999
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,687
Remaining individualsnot grpmax-eligible	0.0256%	3,901
European (non-Finnish)	0.0214%	4,663
South Asian	0.0198%	5,057

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.His642=
Coding: c.1926C>T
MANE Select: NM_020639
dbSNP: rs201057277
Type: single nucleotide variant
Location: chr21:41741267 (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.His642Tyr 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-his642 (accessed [today's date]).

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