Is KDR p.Pro1147Ser (c.3439C>T) pathogenic?

KDR p.Pro1147Ser (c.3439C>T) is classified Pathogenic in KDR (ClinVar, No assertion criteria, 2 submitters; last evaluated 2002-03-01). AlphaMissense: likely benign (0.1946); Ultra-rare (popmax 0.0319%, nfe); Associated with capillary infantile hemangioma.

What condition is associated with KDR p.Pro1147Ser (c.3439C>T)?

KDR p.Pro1147Ser (c.3439C>T) is associated with capillary infantile hemangioma (ClinVar).

How common is KDR p.Pro1147Ser (c.3439C>T) in the general population?

KDR p.Pro1147Ser (c.3439C>T) is ultra-rare (popmax 0.0319%, nfe) (gnomAD).

What do computational predictors say about KDR p.Pro1147Ser (c.3439C>T)?

AlphaMissense predicts likely benign (score 0.1946) — an in-silico prediction, not a clinical call.

KDR p.Pro1147Ser

c.3439C>T · rs121917766 · VCV12317

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary infantile hemangioma

Computational evidence

Protein change
AlphaMissense	0.1946	likely benign ⚠ discordant with ClinVar
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -10.24	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,358 bp · p 5e-06 · regional, not allelic
Overall
CADD	26.5	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 0.0319% European (non-Finnish) · 376/1,179,908 alleles

Filtering AF 0.0292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.025% 403/1,613,886 alleles · ultra-rare exomes 391/1,461,722 · genomes 12/152,164 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0319%	3,138
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Admixed American	0.0133%	7,501
African / African-American	0.00935%	10,699

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.Pro1147Ser
Coding: c.3439C>T
MANE Select: NM_002253
dbSNP: rs121917766
Type: single nucleotide variant
Location: chr4:55088939 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 1147: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in hci; somatic mutation)

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.Pro1147= Uncertain significance same residue
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

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-pro1147ser (accessed [today's date]).

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