Is KDR p.Val136Met (c.406G>A) pathogenic?

KDR p.Val136Met (c.406G>A) is classified Benign in KDR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-10-10). AlphaMissense: likely benign (0.2631); Low-frequency (popmax 1.37%, eas).

How common is KDR p.Val136Met (c.406G>A) in the general population?

KDR p.Val136Met (c.406G>A) is low-frequency (popmax 1.37%, eas) (gnomAD).

What do computational predictors say about KDR p.Val136Met (c.406G>A)?

AlphaMissense predicts likely benign (score 0.2631) — an in-silico prediction, not a clinical call.

KDR p.Val136Met

c.406G>A · rs35636987 · VCV134611

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2631 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2631	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.14	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 2.6	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	24.0	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 1.37% East Asian · 611/44,554 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 0.0478% 743/1,555,858 alleles · low-frequency exomes 674/1,403,688 · genomes 69/152,170 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.37%	73
Remaining individualsnot grpmax-eligible	0.0992%	1,008
South Asian	0.0222%	4,499
Admixed American	0.01%	9,982
Finnishnot grpmax-eligible	0.00782%	12,791
European (non-Finnish)	0.00364%	27,490

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.Val136Met
Coding: c.406G>A
MANE Select: NM_002253
dbSNP: rs35636987
Type: single nucleotide variant
Location: chr4:55115364 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 136: a UniProt-annotated variant site (in); a β-strand

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-val136met (accessed [today's date]).

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