Is KDR p.Cys482Arg (c.1444T>C) pathogenic?

KDR p.Cys482Arg (c.1444T>C) is classified Likely benign in KDR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-07-07). AlphaMissense: likely pathogenic (0.751); Low-frequency (popmax 3.58%, mid); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Cys482Arg (c.1444T>C)?

KDR p.Cys482Arg (c.1444T>C) is associated with capillary infantile hemangioma (ClinVar).

How common is KDR p.Cys482Arg (c.1444T>C) in the general population?

KDR p.Cys482Arg (c.1444T>C) is low-frequency (popmax 3.58%, mid) (gnomAD).

What do computational predictors say about KDR p.Cys482Arg (c.1444T>C)?

AlphaMissense predicts likely pathogenic (score 0.751) — an in-silico prediction, not a clinical call.

KDR p.Cys482Arg

c.1444T>C · rs34231037 · VCV12318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.751 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.58%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.751	likely pathogenic
REVEL	0.74	pathogenic-leaning
SaProt	LLR -9.19	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	23.8	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 3.58% Middle Eastern · 216/6,038 alleles

Filtering AF 3.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.15%

Overall 2.77% 44,363/1,602,386 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	11.4%	9
Finnishnot grpmax-eligible	4.21%	24
Middle Easterngrpmax	3.58%	28
European (non-Finnish)	3.19%	31
Remaining individualsnot grpmax-eligible	2.58%	39
Ashkenazi Jewishnot grpmax-eligible	1.8%	55
Admixed American	1.37%	73
South Asian	0.741%	135
African / African-American	0.544%	184
East Asian	0.00223%	44,768

Amish 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.Cys482Arg
Coding: c.1444T>C
MANE Select: NM_002253
dbSNP: rs34231037
Type: single nucleotide variant
Location: chr4:55106779 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 482: a β-strand; a disulfide bond; a UniProt-annotated variant site (probable risk factor for hci; expression of flt1 in hemangioma endothelial cells is markedly reduced and kdr activity is increased compared to controls; low flt1 expression in hemangioma cells is caused by reduced activity of a pathway involving itgb1, antxr1, kdr and nfatc2ip; the mutation predicts to result in loss-of-function and disruption of the normal association of these molecules); the ig-like c2-type 5 domain

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.Glu372Asp Benign ★★ ⚠ same condition
KDR p.Thr771Met Likely benign ★★ same condition
KDR p.Ala1065Thr Uncertain significance ★ ⚠ same condition
KDR p.Arg946His 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-cys482arg (accessed [today's date]).

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