Is KDR p.Glu372Asp (c.1116G>C) pathogenic?

KDR p.Glu372Asp (c.1116G>C) is classified Benign in KDR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-30). AlphaMissense: likely benign (0.0878); Low-frequency (popmax 2.53%, afr); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Glu372Asp (c.1116G>C)?

KDR p.Glu372Asp (c.1116G>C) is associated with capillary infantile hemangioma (ClinVar).

How common is KDR p.Glu372Asp (c.1116G>C) in the general population?

KDR p.Glu372Asp (c.1116G>C) is low-frequency (popmax 2.53%, afr) (gnomAD).

What do computational predictors say about KDR p.Glu372Asp (c.1116G>C)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

KDR p.Glu372Asp

c.1116G>C · rs113121239 · VCV134619

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.53%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -2.4, phastCons 0.28
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	14.91	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 2.53% African / African-American · 1,899/74,980 alleles

Filtering AF 2.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.4%

Overall 0.133% 2,147/1,613,908 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.53%	39
Admixed American	0.17%	588
Remaining individualsnot grpmax-eligible	0.158%	631
Middle Eastern	0.116%	865
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
South Asian	0.00439%	22,767
European (non-Finnish)	0.00237%	42,140

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.Glu372Asp
Coding: c.1116G>C
MANE Select: NM_002253
dbSNP: rs113121239
Type: single nucleotide variant
Location: chr4:55110542 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 372: the ig-like c2-type 4 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.Cys482Arg Likely 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-glu372asp (accessed [today's date]).

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