Is KL p.Pro954= (c.2862G>C) pathogenic?

KL p.Pro954= (c.2862G>C) is classified Likely benign in KL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-22). Very rare (popmax 6.2e-05%); Associated with KL-related disorder.

What condition is associated with KL p.Pro954= (c.2862G>C)?

KL p.Pro954= (c.2862G>C) is associated with KL-related disorder (ClinVar).

How common is KL p.Pro954= (c.2862G>C) in the general population?

KL p.Pro954= (c.2862G>C) is very rare (popmax 6.2e-05%) (gnomAD).

KL p.Pro954=

c.2862G>C · VCV3346822

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

KL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.5	GERP -3.2
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,098 alleles · very rare exomes 1/1,461,892 · genomes 0/152,206 · 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: KL
Protein: p.Pro954=
Coding: c.2862G>C
MANE Select: NM_004795
Type: single nucleotide variant
Location: chr13:33064009 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB
Residue 954: a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)

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

Disease context

KL-related disorder

Similar variants

KL p.Pro954Leu Uncertain significance ★ ⚠ same residue
KL c.1331-3C>A Uncertain significance ★★ same type
KL p.Ala3Thr Uncertain significance ★★ ⚠ same type
KL p.Ala50Val Uncertain significance ★★ ⚠ same type
KL p.Ala656Thr Uncertain significance ★★ ⚠ same type
KL p.Ala663Thr Uncertain significance ★★ ⚠ same type
KL p.Ala987Thr Uncertain significance ★★ ⚠ same type
KL p.Arg179Trp 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/kl-p-pro954 (accessed [today's date]).

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