Is KDR p.Gly550Cys (c.1648G>T) pathogenic?

KDR p.Gly550Cys (c.1648G>T) is classified Uncertain significance in KDR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: ambiguous (0.49); Very rare (popmax 0.00936%, afr).

How common is KDR p.Gly550Cys (c.1648G>T) in the general population?

KDR p.Gly550Cys (c.1648G>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about KDR p.Gly550Cys (c.1648G>T)?

AlphaMissense predicts ambiguous (score 0.49) — an in-silico prediction, not a clinical call.

KDR p.Gly550Cys

c.1648G>T · VCV3288006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.49 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Computational evidence

Protein change
AlphaMissense	0.49	ambiguous
REVEL	0.509	indeterminate
SaProt	LLR -10.25	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	26.0	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 0.00936% African / African-American · 7/74,786 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,612,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,684
European (non-Finnish)	8.48e-05%	1,178,971

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.Gly550Cys
Coding: c.1648G>T
MANE Select: NM_002253
Type: single nucleotide variant
Location: chr4:55104982 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB

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

Similar variants

KDR p.Ala379Val Uncertain significance ★★ ⚠ same type
KDR p.Ala757Gly Uncertain significance ★★ ⚠ same type
KDR p.Asp832His Uncertain significance ★★ ⚠ same type
KDR p.Val416Ala Uncertain significance ★★ ⚠ same type
KDR p.Ala1030= Benign ★★ same type
KDR p.Ala532= Benign ★★ same type
KDR p.Arg842His Likely benign ★★ ⚠ same type
KDR p.Cys482Arg Likely benign ★★ same type

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-gly550cys (accessed [today's date]).

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