Is ARSI p.Asp165= (c.495C>T) pathogenic?

ARSI p.Asp165= (c.495C>T) is classified Likely benign in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-27). Ultra-rare (popmax 0.0316%, nfe); Associated with Spastic paraplegia.

What condition is associated with ARSI p.Asp165= (c.495C>T)?

ARSI p.Asp165= (c.495C>T) is associated with Spastic paraplegia (ClinVar).

How common is ARSI p.Asp165= (c.495C>T) in the general population?

ARSI p.Asp165= (c.495C>T) is ultra-rare (popmax 0.0316%, nfe) (gnomAD).

ARSI p.Asp165=

c.495C>T · rs767783947 · VCV788727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0316%, nfe)

Conditions

Spastic paraplegia

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 2.6	GERP -1.6, phastCons 1
Overall
CADD	7.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0316% European (non-Finnish) · 373/1,180,054 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.0252% 406/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0316%	3,164
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.0133%	7,501
African / African-American	0.00667%	14,987
Finnishnot grpmax-eligible	0.00312%	32,019

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: ARSI
Protein: p.Asp165=
Coding: c.495C>T
MANE Select: NM_001012301
dbSNP: rs767783947
Type: single nucleotide variant
Location: chr5:150298429 (GRCh38)
Gene constraint: LOEUF 1.403 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.35

Full ARSI 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

ARSI p.Ala216Thr Uncertain significance ★★ ⚠ same condition
ARSI p.Ala259Val Uncertain significance ★★ ⚠ same condition
ARSI p.Ala264Thr Uncertain significance ★★ ⚠ same condition
ARSI p.Ala399Asp Uncertain significance ★★ ⚠ same condition
ARSI p.Ala414Ser Uncertain significance ★★ ⚠ same condition
ARSI p.Ala414Thr Uncertain significance ★★ ⚠ same condition
ARSI p.Ala78Thr Uncertain significance ★★ ⚠ same condition
ARSI p.Arg117Cys 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/arsi-p-asp165 (accessed [today's date]).

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