Is ARSI p.Asp372= (c.1116C>T) pathogenic?

ARSI p.Asp372= (c.1116C>T) is classified Likely benign in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). Ultra-rare (popmax 0.0996%, mid); Associated with Spastic paraplegia.

What condition is associated with ARSI p.Asp372= (c.1116C>T)?

ARSI p.Asp372= (c.1116C>T) is associated with Spastic paraplegia (ClinVar).

How common is ARSI p.Asp372= (c.1116C>T) in the general population?

ARSI p.Asp372= (c.1116C>T) is ultra-rare (popmax 0.0996%, mid) (gnomAD).

ARSI p.Asp372=

c.1116C>T · rs190469665 · VCV3017674

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0996%, mid)

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 -7.2	GERP -5.1
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0996% Middle Eastern · 6/6,026 alleles

Filtering AF 0.0511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0463%

Overall 0.0103% 165/1,606,196 alleles · ultra-rare exomes 155/1,453,934 · genomes 10/152,262 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0996%	1,004
South Asian	0.0644%	1,553
European (non-Finnish)	0.00774%	12,921
Admixed American	0.00671%	14,906
Remaining individualsnot grpmax-eligible	0.00644%	15,540
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,076
African / African-American	0.00134%	74,900

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.Asp372=
Coding: c.1116C>T
MANE Select: NM_001012301
dbSNP: rs190469665
Type: single nucleotide variant
Location: chr5:150297808 (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.Asp372Asn Uncertain significance ★★ ⚠ same residue
ARSI p.Asp372His Uncertain significance ★ ⚠ same residue
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

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-asp372 (accessed [today's date]).

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