Is KDR p.Val416Ala (c.1247T>C) pathogenic?

KDR p.Val416Ala (c.1247T>C) is classified Uncertain significance in KDR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-25). AlphaMissense: likely benign (0.0808); Very rare (popmax 0.00534%, afr); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Val416Ala (c.1247T>C)?

KDR p.Val416Ala (c.1247T>C) is associated with capillary infantile hemangioma (ClinVar).

How common is KDR p.Val416Ala (c.1247T>C) in the general population?

KDR p.Val416Ala (c.1247T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about KDR p.Val416Ala (c.1247T>C)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

KDR p.Val416Ala

c.1247T>C · rs751603128 · VCV3113923

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.60 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.5	GERP 0.41, phastCons 0.51
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	16.24	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 0.00534% African / African-American · 4/74,912 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00372% 60/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
European (non-Finnish)	0.00475%	21,070

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.Val416Ala
Coding: c.1247T>C
MANE Select: NM_002253
dbSNP: rs751603128
Type: single nucleotide variant
Location: chr4:55110411 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 416: a β-strand

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.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
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-val416ala (accessed [today's date]).

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