Is KLC2 p.Asp362= (c.1086C>T) pathogenic?

KLC2 p.Asp362= (c.1086C>T) is classified Benign in KLC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 49.7%, amr) — too common for a highly-penetrant pathogenic allele; Associated with spastic paraplegia, optic atropy, and neuropathy.

What condition is associated with KLC2 p.Asp362= (c.1086C>T)?

KLC2 p.Asp362= (c.1086C>T) is associated with spastic paraplegia, optic atropy, and neuropathy (ClinVar).

KLC2 p.Asp362=

Q: How common is KLC2 p.Asp362= (c.1086C>T) in the general population?

KLC2 p.Asp362= (c.1086C>T) is common (popmax 49.7%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Spastic paraplegia-optic atrophy-neuropathy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1086C>T · rs1151539 · VCV1300079

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 49.7%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

spastic paraplegia, optic atropy, and neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.6, phastCons 1
Overall
CADD	7.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.7% Admixed American · 26,180/52,708 alleles

Filtering AF 49.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 49%

Overall 45.1% 707,906/1,568,692 alleles · common exomes 646,751/1,416,714 · genomes 61,155/151,978 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	53.7%	2
Finnishnot grpmax-eligible	52.1%	2
Admixed Americangrpmax	49.7%	2
European (non-Finnish)	47.6%	2
Ashkenazi Jewishnot grpmax-eligible	46%	2
Remaining individualsnot grpmax-eligible	42.9%	2
Middle Eastern	38.4%	3
South Asian	34.7%	3
East Asian	25.4%	4
African / African-American	23.6%	4

Amish 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: KLC2
Protein: p.Asp362=
Coding: c.1086C>T
MANE Select: NM_001318734
dbSNP: rs1151539
Type: single nucleotide variant
Location: chr11:66264189 (GRCh38)
Gene constraint: LOEUF 0.616 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79 · 2 PDB

Full KLC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spastic paraplegia, optic atropy, and neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spastic paraplegia-optic atrophy-neuropathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

KLC2 p.Arg509Gln Uncertain significance ★★ ⚠ same condition
KLC2 c.1444-24C>T Benign ★★ same condition
KLC2 c.942+27T>C Benign ★★ same condition
KLC2 c.-451_-235del Pathogenic same condition
KLC2 p.Arg110His Uncertain significance ★★ ⚠ same type
KLC2 p.Arg418Gln Uncertain significance ★★ ⚠ same type
KLC2 p.Arg418Trp Uncertain significance ★★ ⚠ same type
KLC2 p.Arg479His 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/klc2-p-asp362 (accessed [today's date]).

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