Is KDR p.Phe170Leu (c.508T>C) pathogenic?

KDR p.Phe170Leu (c.508T>C) is classified Uncertain significance in KDR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely pathogenic (0.9056); Very rare (popmax 0.00133%, afr).

How common is KDR p.Phe170Leu (c.508T>C) in the general population?

KDR p.Phe170Leu (c.508T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about KDR p.Phe170Leu (c.508T>C)?

AlphaMissense predicts likely pathogenic (score 0.9056) — an in-silico prediction, not a clinical call.

KDR p.Phe170Leu

c.508T>C · VCV3863567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9056 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9056	likely pathogenic
REVEL	0.109	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	19.32	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 0.00133% African / African-American · 1/74,926 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,446 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,926
European (non-Finnish)	0.00017%	589,790

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.Phe170Leu
Coding: c.508T>C
MANE Select: NM_002253
Type: single nucleotide variant
Location: chr4:55115024 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 170: a β-strand; a disulfide bond; the ig-like c2-type 2 domain

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

Similar variants

KDR p.Phe170Cys Uncertain significance ★ ⚠ same residue
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

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-phe170leu (accessed [today's date]).

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