Is KDR p.Arg842His (c.2525G>A) pathogenic?

KDR p.Arg842His (c.2525G>A) is classified Likely benign in KDR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-07). AlphaMissense: likely benign (0.1594); Ultra-rare (popmax 0.0174%, afr); Associated with hepatoblastoma.

What condition is associated with KDR p.Arg842His (c.2525G>A)?

KDR p.Arg842His (c.2525G>A) is associated with hepatoblastoma (ClinVar).

How common is KDR p.Arg842His (c.2525G>A) in the general population?

KDR p.Arg842His (c.2525G>A) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

How is Hepatoblastoma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KDR p.Arg842His (c.2525G>A)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

KDR p.Arg842His

c.2525G>A · rs149901681 · VCV1110788

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hepatoblastoma

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.438	indeterminate
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,468 bp · p 9.5e-05 · regional, not allelic
Overall
CADD	26.6	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 0.0174% African / African-American · 13/74,682 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0143% 231/1,612,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,745
European (non-Finnish)	0.0173%	5,779
Middle Eastern	0.0164%	6,080
Admixed American	0.0134%	7,483
Remaining individualsnot grpmax-eligible	0.00481%	20,801
South Asian	0.0022%	45,500

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: KDR
Protein: p.Arg842His
Coding: c.2525G>A
MANE Select: NM_002253
dbSNP: rs149901681
Type: single nucleotide variant
Location: chr4:55097751 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 842: the protein kinase domain; a β-strand; a binding site

Full KDR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hepatoblastoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hepatoblastoma (Orphanet):

Inheritance: Not applicable
Onset: Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

KDR p.Ala379Val Uncertain significance ★★ ⚠ same type
KDR p.Ala757Gly Uncertain significance ★★ ⚠ same type
KDR p.Asp832His Uncertain significance ★★ ⚠ same type
KDR p.Val416Ala Uncertain significance ★★ ⚠ same type
KDR p.Ala1030= Benign ★★ same type
KDR p.Ala532= Benign ★★ same type
KDR p.Cys482Arg Likely benign ★★ same type
KDR p.Glu372Asp Benign ★★ ⚠ 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/kdr-p-arg842his (accessed [today's date]).

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