Is KEL p.Val48Glu (c.143T>A) pathogenic?

KEL p.Val48Glu (c.143T>A) is classified Uncertain significance in KEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.2297); Ultra-rare (popmax 0.0117%, amr).

How common is KEL p.Val48Glu (c.143T>A) in the general population?

KEL p.Val48Glu (c.143T>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about KEL p.Val48Glu (c.143T>A)?

AlphaMissense predicts likely benign (score 0.2297) — an in-silico prediction, not a clinical call.

KEL p.Val48Glu

c.143T>A · VCV3533264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2297	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP -1.9
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.95 · regional, not allelic
Overall
CADD	10.28	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 0.0117% Admixed American · 7/59,736 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.000434% 7/1,611,932 alleles · ultra-rare exomes 5/1,459,814 · genomes 2/152,118 · 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.Val48Glu
Coding: c.143T>A
MANE Select: NM_000420
Type: single nucleotide variant
Location: chr7:142961440 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.46

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-val48glu (accessed [today's date]).

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