Is KDR p.Ala379Val (c.1136C>T) pathogenic?

KDR p.Ala379Val (c.1136C>T) is classified Uncertain significance in KDR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-17). AlphaMissense: likely benign (0.0632); Ultra-rare (popmax 0.0493%, mid); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Ala379Val (c.1136C>T)?

KDR p.Ala379Val (c.1136C>T) is associated with capillary infantile hemangioma, tufted angioma (ClinVar).

How common is KDR p.Ala379Val (c.1136C>T) in the general population?

KDR p.Ala379Val (c.1136C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about KDR p.Ala379Val (c.1136C>T)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

KDR p.Ala379Val

c.1136C>T · rs747477930 · VCV2672213

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -5.46	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 3.1	GERP 0.25, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	7.124	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 0.0493% Middle Eastern · 3/6,082 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00905% 146/1,613,658 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
Admixed American	0.045%	2,221
South Asian	0.0406%	2,461
Remaining individualsnot grpmax-eligible	0.0192%	5,206
African / African-American	0.0174%	5,757
Finnishnot grpmax-eligible	0.0109%	9,139
East Asian	0.00668%	14,960
European (non-Finnish)	0.00373%	26,815

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.Ala379Val
Coding: c.1136C>T
MANE Select: NM_002253
dbSNP: rs747477930
Type: single nucleotide variant
Location: chr4:55110522 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 379: a β-strand; 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

Also linked: tufted angioma

Similar variants

KDR p.Ala379= Likely benign ★ same residue
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-ala379val (accessed [today's date]).

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