Is KDR p.Leu1002Phe (c.3006G>C) pathogenic?

KDR p.Leu1002Phe (c.3006G>C) is classified Uncertain significance in KDR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1935); Very rare (popmax 0.000593%, nfe); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Leu1002Phe (c.3006G>C)?

KDR p.Leu1002Phe (c.3006G>C) is associated with capillary infantile hemangioma (ClinVar).

How common is KDR p.Leu1002Phe (c.3006G>C) in the general population?

KDR p.Leu1002Phe (c.3006G>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about KDR p.Leu1002Phe (c.3006G>C)?

AlphaMissense predicts likely benign (score 0.1935) — an in-silico prediction, not a clinical call.

KDR p.Leu1002Phe

c.3006G>C · rs1041785569 · VCV1710210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.1935	likely benign
REVEL	0.564	indeterminate
SaProt	LLR -8.74	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 2.3	GERP 0.81, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,468 bp · p 9.5e-05 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,834 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,610 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)grpmax	0.000593%	168,548

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu1002Phe
Coding: c.3006G>C
MANE Select: NM_002253
dbSNP: rs1041785569
Type: single nucleotide variant
Location: chr4:55092680 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 1002: the protein kinase domain; an α-helix

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

Disease context

capillary infantile hemangioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDR p.Ala379Val Uncertain significance ★★ ⚠ same condition
KDR p.Ala757Gly Uncertain significance ★★ ⚠ same condition
KDR p.Asp832His Uncertain significance ★★ ⚠ same condition
KDR p.Val416Ala Uncertain significance ★★ ⚠ same condition
KDR p.Cys482Arg Likely benign ★★ same condition
KDR p.Glu372Asp Benign ★★ ⚠ same condition
KDR p.Thr771Met Likely benign ★★ same condition
KDR p.Ala1065Thr 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/kdr-p-leu1002phe (accessed [today's date]).

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