Is KDR p.Leu242Phe (c.724C>T) pathogenic?

KDR p.Leu242Phe (c.724C>T) is classified Likely pathogenic in KDR (ClinVar, Single submitter, 2 submitters; last evaluated 2020-03-02). AlphaMissense: ambiguous (0.5523); Very rare (popmax 0.00134%, afr); Associated with primary ovarian failure.

What condition is associated with KDR p.Leu242Phe (c.724C>T)?

KDR p.Leu242Phe (c.724C>T) is associated with primary ovarian failure (ClinVar).

How common is KDR p.Leu242Phe (c.724C>T) in the general population?

KDR p.Leu242Phe (c.724C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about KDR p.Leu242Phe (c.724C>T)?

AlphaMissense predicts ambiguous (score 0.5523) — an in-silico prediction, not a clinical call.

KDR p.Leu242Phe

c.724C>T · rs587778428 · VCV134612

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

primary ovarian failure

Computational evidence

Protein change
AlphaMissense	0.5523	ambiguous
REVEL	0.512	indeterminate
SaProt	LLR -11.62	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 23 kb · p 0.092 · regional, not allelic
Overall
CADD	26.9	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 0.00134% African / African-American · 1/74,882 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,754 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,882
European (non-Finnish)	0.000254%	393,287

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.Leu242Phe
Coding: c.724C>T
MANE Select: NM_002253
dbSNP: rs587778428
Type: single nucleotide variant
Location: chr4:55114200 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 242: a β-strand; the ig-like c2-type 3 domain

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

Disease context

primary ovarian failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu242phe (accessed [today's date]).

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