Is KEL p.Glu413Asp (c.1239G>T) pathogenic?

KEL p.Glu413Asp (c.1239G>T) is classified Uncertain significance in KEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1007); Very rare (popmax 8.47e-05%, nfe).

How common is KEL p.Glu413Asp (c.1239G>T) in the general population?

KEL p.Glu413Asp (c.1239G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about KEL p.Glu413Asp (c.1239G>T)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

KEL p.Glu413Asp

c.1239G>T · VCV4091476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.97	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 -0.9	GERP -6.3, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.95 · regional, not allelic
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.2e-05% 1/1,614,126 alleles · very rare exomes 1/1,461,816 · genomes 0/152,310 · joint denominator

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: KEL
Protein: p.Glu413Asp
Coding: c.1239G>T
MANE Select: NM_000420
Type: single nucleotide variant
Location: chr7:142946282 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.46
Residue 413: the peptidase m13 domain

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

Similar variants

KEL p.Pro375Thr Uncertain significance ★★ ⚠ same type
KEL p.Arg516= Benign ★★ same type
KEL p.Leu335= Likely benign ★★ same type
KEL p.Leu597Pro Benign ★★ same type
KEL p.Phe324= Benign ★★ same type
KEL c.400+1G>A Pathogenic ★ same type
KEL p.Ala148Gly Uncertain significance ★ ⚠ same type
KEL p.Ala311Asp Uncertain significance ★ ⚠ 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/kel-p-glu413asp (accessed [today's date]).

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