Is KDR p.Ile915Val (c.2743A>G) pathogenic?

KDR p.Ile915Val (c.2743A>G) is classified Likely benign in KDR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-30). AlphaMissense: likely benign (0.1526); Ultra-rare (popmax 0.0135%, nfe).

How common is KDR p.Ile915Val (c.2743A>G) in the general population?

KDR p.Ile915Val (c.2743A>G) is ultra-rare (popmax 0.0135%, nfe) (gnomAD).

What do computational predictors say about KDR p.Ile915Val (c.2743A>G)?

AlphaMissense predicts likely benign (score 0.1526) — an in-silico prediction, not a clinical call.

KDR p.Ile915Val

c.2743A>G · rs140228618 · VCV695564

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1526 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1526	likely benign
REVEL	0.498	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,468 bp · p 9.5e-05 · regional, not allelic
Overall
CADD	25.6	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 0.0135% European (non-Finnish) · 159/1,179,332 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.0114% 184/1,613,132 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,557
European (non-Finnish)grpmax	0.0135%	7,417
Finnishnot grpmax-eligible	0.00625%	16,004
Remaining individualsnot grpmax-eligible	0.0032%	31,224

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile915Val
Coding: c.2743A>G
MANE Select: NM_002253
dbSNP: rs140228618
Type: single nucleotide variant
Location: chr4:55095651 (GRCh38)
Gene constraint: LOEUF 0.328 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.67 · 54 PDB
Residue 915: the protein kinase domain; 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-ile915val (accessed [today's date]).

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