Is JKAMP p.Phe293fs (c.878del) pathogenic?

JKAMP p.Phe293fs (c.878del) is classified Uncertain significance in JKAMP (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-29). Very rare (popmax 0.00134%, afr); Associated with JKAMP neurodevelopmental disorder.

What condition is associated with JKAMP p.Phe293fs (c.878del)?

JKAMP p.Phe293fs (c.878del) is associated with JKAMP neurodevelopmental disorder, neurodevelopmental disorder with seizures and impaired intellectual and language development (ClinVar).

How common is JKAMP p.Phe293fs (c.878del) in the general population?

JKAMP p.Phe293fs (c.878del) is very rare (popmax 0.00134%, afr) (gnomAD).

JKAMP p.Phe293fs

c.878del · VCV4072203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

JKAMP neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -2.3, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,862 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,613,554 alleles · very rare exomes 5/1,461,552 · genomes 2/152,002 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,862
European (non-Finnish)	0.000509%	196,628

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: JKAMP
Protein: p.Phe293fs
Coding: c.878del
MANE Select: NM_016475
Type: Deletion
Location: chr14:59504013 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 86.76

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

Disease context

JKAMP neurodevelopmental disorder

Also linked: neurodevelopmental disorder with seizures and impaired intellectual and language development

Similar variants

JKAMP c.458+1G>C Likely pathogenic ★ same condition
JKAMP c.640+1G>T Likely pathogenic ★ same condition
JKAMP p.Gln47Ter Likely pathogenic ★ same condition
JKAMP p.Leu19Ter Likely pathogenic ★ same condition
JKAMP p.Arg188Ter Uncertain significance ★ same condition
JKAMP p.Asp127Gly Uncertain significance ★ ⚠ same condition
JKAMP p.Glu148Gly Uncertain significance ★ ⚠ same condition
JKAMP p.Gly37Glu Uncertain significance ★ ⚠ same condition

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/jkamp-p-phe293fs (accessed [today's date]).

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