Is L1CAM p.Val577= (c.1731C>T) pathogenic?

L1CAM p.Val577= (c.1731C>T) is classified Likely benign in L1CAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-06). Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with L1CAM p.Val577= (c.1731C>T)?

L1CAM p.Val577= (c.1731C>T) is associated with Spastic paraplegia (ClinVar).

How common is L1CAM p.Val577= (c.1731C>T) in the general population?

L1CAM p.Val577= (c.1731C>T) is absent from gnomAD v4.1 (gnomAD).

L1CAM p.Val577=

c.1731C>T · rs2520997360 · VCV2093986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.044	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.59, phastCons 1
Overall
CADD	12.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: L1CAM
Protein: p.Val577=
Coding: c.1731C>T
MANE Select: NM_001278116
dbSNP: rs2520997360
Type: single nucleotide variant
Location: chrX:153868095 (GRCh38)
Structure: AlphaFold pLDDT 78.82 · 2 PDB
Residue 577: the ig-like c2-type 6 domain; a UniProt-annotated variant site (found in l1 syndrome; likely pathogenic)

Full L1CAM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

L1CAM c.2431+5G>A Pathogenic/Likely pathogenic ★★ same condition
L1CAM c.2872+1G>A Pathogenic ★★ same condition
L1CAM c.3531-12G>A Pathogenic/Likely pathogenic ★★ same condition
L1CAM c.400+5G>A Pathogenic/Likely pathogenic ★★ same condition
L1CAM c.806+1G>C Pathogenic ★★ same condition
L1CAM c.807-6G>A Pathogenic/Likely pathogenic ★★ same condition
L1CAM c.92-1G>A Pathogenic/Likely pathogenic ★★ same condition
L1CAM p.Glu309Lys Pathogenic/Likely pathogenic ★★ 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/l1cam-p-val577 (accessed [today's date]).

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