Is KDR p.Val297Ile (c.889G>A) pathogenic?

KDR p.Val297Ile (c.889G>A) is classified Benign in KDR (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-08-02). AlphaMissense: likely benign (0.0895); Common (popmax 23.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with KDR-related disorder.

What condition is associated with KDR p.Val297Ile (c.889G>A)?

KDR p.Val297Ile (c.889G>A) is associated with KDR-related disorder (ClinVar).

What do computational predictors say about KDR p.Val297Ile (c.889G>A)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

KDR p.Val297Ile

Q: How common is KDR p.Val297Ile (c.889G>A) in the general population?

KDR p.Val297Ile (c.889G>A) is common (popmax 23.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.889G>A · rs2305948 · VCV134616

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 23.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KDR-related disorder

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.41	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 0.6	GERP 1.5, phastCons 0.098
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	18.05	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 23.9% African / African-American · 17,931/74,950 alleles

Filtering AF 23.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.5%

Overall 10.5% 169,367/1,613,886 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	23.9%	4
East Asian	12.9%	8
Remaining individualsnot grpmax-eligible	11.1%	9
South Asian	10.3%	10
Middle Eastern	10.3%	10
Ashkenazi Jewishnot grpmax-eligible	9.94%	10
European (non-Finnish)	9.81%	10
Finnishnot grpmax-eligible	8.87%	11
Amishnot grpmax-eligible	7.89%	13
Admixed American	7.02%	14

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.Val297Ile
Coding: c.889G>A
MANE Select: NM_002253
dbSNP: rs2305948
Type: single nucleotide variant
Location: chr4:55113391 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 297: a disulfide bond; a UniProt-annotated variant site (in); the ig-like c2-type 3 domain

Full KDR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KDR-related disorder

Similar variants

KDR p.Gly1092Arg Uncertain significance ⚠ same condition
KDR c.1537-6G>A Likely benign same condition
KDR c.3510+10C>T Likely benign same condition
KDR c.-1G>T Benign same condition
KDR p.Gln472His Benign same condition
KDR p.Gly1283= Likely benign same condition
KDR p.Ile1330Leu Benign same condition
KDR p.Lys941= 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-val297ile (accessed [today's date]).

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