Is KDR p.Val547Met (c.1639G>A) pathogenic?

KDR p.Val547Met (c.1639G>A) is classified Uncertain significance in KDR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely pathogenic (0.7314); Ultra-rare (popmax 0.0132%, sas).

How common is KDR p.Val547Met (c.1639G>A) in the general population?

KDR p.Val547Met (c.1639G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about KDR p.Val547Met (c.1639G>A)?

AlphaMissense predicts likely pathogenic (score 0.7314) — an in-silico prediction, not a clinical call.

KDR p.Val547Met

c.1639G>A · rs761405036 · VCV3113926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7314	likely pathogenic
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	25.9	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 0.0132% South Asian · 12/90,720 alleles

Filtering AF 0.00753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00595%

Overall 0.00263% 42/1,595,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,560
Remaining individualsnot grpmax-eligible	0.00485%	20,626
European (non-Finnish)	0.00232%	43,071

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.Val547Met
Coding: c.1639G>A
MANE Select: NM_002253
dbSNP: rs761405036
Type: single nucleotide variant
Location: chr4:55105838 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 547: a β-strand; the ig-like c2-type 5 domain

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-val547met (accessed [today's date]).

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