Is KDR p.Ala352Val (c.1055C>T) pathogenic?

KDR p.Ala352Val (c.1055C>T) is classified Benign in KDR (ClinVar, Single submitter, 2 submitters; last evaluated 2018-07-31). AlphaMissense: likely benign (0.0499); Rare (popmax 0.499%, afr).

How common is KDR p.Ala352Val (c.1055C>T) in the general population?

KDR p.Ala352Val (c.1055C>T) is rare (popmax 0.499%, afr) (gnomAD).

What do computational predictors say about KDR p.Ala352Val (c.1055C>T)?

AlphaMissense predicts likely benign (score 0.0499) — an in-silico prediction, not a clinical call.

KDR p.Ala352Val

c.1055C>T · rs151317075 · VCV134617

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0499 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.499%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0499	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -7.21	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 8.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	17.07	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 0.499% African / African-American · 373/74,778 alleles

Filtering AF 0.457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.441%

Overall 0.0285% 459/1,613,304 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.499%	200
Middle Eastern	0.0826%	1,211
Admixed American	0.0367%	2,725
Remaining individualsnot grpmax-eligible	0.0272%	3,676
South Asian	0.00879%	11,378
East Asian	0.00446%	22,422
European (non-Finnish)	0.00271%	36,870

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.Ala352Val
Coding: c.1055C>T
MANE Select: NM_002253
dbSNP: rs151317075
Type: single nucleotide variant
Location: chr4:55110690 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 352: the ig-like c2-type 4 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-ala352val (accessed [today's date]).

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