Is KDR p.Pro956= (c.2868T>G) pathogenic?

KDR p.Pro956= (c.2868T>G) is classified Likely benign in KDR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). Ultra-rare (popmax 0.0201%, eas); Associated with KDR-related disorder.

What condition is associated with KDR p.Pro956= (c.2868T>G)?

KDR p.Pro956= (c.2868T>G) is associated with KDR-related disorder (ClinVar).

How common is KDR p.Pro956= (c.2868T>G) in the general population?

KDR p.Pro956= (c.2868T>G) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

KDR p.Pro956=

c.2868T>G · rs759473733 · VCV3058767

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Conditions

KDR-related disorder

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 -1.7	GERP -5.5
Overall
CADD	0.525	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,870 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00124% 20/1,613,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
Remaining individualsnot grpmax-eligible	0.0144%	6,941
Admixed American	0.00167%	59,996
European (non-Finnish)	8.48e-05%	1,179,902

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.Pro956=
Coding: c.2868T>G
MANE Select: NM_002253
dbSNP: rs759473733
Type: single nucleotide variant
Location: chr4:55094905 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 956: the protein kinase domain

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

Disease context

KDR-related disorder

Similar variants

KDR p.Gly1092Arg Uncertain significance ⚠ same condition
KDR c.1537-6G>A Likely benign same condition
KDR c.3510+10C>T Likely benign same condition
KDR c.-1G>T Benign same condition
KDR p.Gln472His Benign same condition
KDR p.Gly1283= Likely benign same condition
KDR p.Ile1330Leu Benign same condition
KDR p.Lys941= Likely benign 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/kdr-p-pro956 (accessed [today's date]).

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