Is SACS p.Arg2002fs (c.6002_6003dup) pathogenic?

SACS p.Arg2002fs (c.60026003dup) is classified Pathogenic in SACS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-20). No gnomAD frequency available for this variant; Associated with Spastic paraplegia.

What condition is associated with SACS p.Arg2002fs (c.6002_6003dup)?

SACS p.Arg2002fs (c.6002_6003dup) is associated with Spastic paraplegia (ClinVar).

How common is SACS p.Arg2002fs (c.6002_6003dup) in the general population?

SACS p.Arg2002fs (c.6002_6003dup) is no gnomAD frequency available for this variant (gnomAD).

SACS p.Arg2002fs

c.6002_6003dup · rs2542257262 · VCV2857858

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Spastic paraplegia

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 (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 1.9, phastCons 0.95

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SACS
Protein: p.Arg2002fs
Coding: c.6002_6003dup
MANE Select: NM_014363
dbSNP: rs2542257262
Type: Duplication
Location: chr13:23337872 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full SACS 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

SACS p.Arg2002= Likely benign ★ same residue
SACS p.Ala2180fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg2932fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Arg3792fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn1094fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asn3040fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Asp2796fs Pathogenic/Likely pathogenic ★★ same condition
SACS p.Glu2280fs 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/sacs-p-arg2002fs (accessed [today's date]).

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