Is ARSI p.Pro310= (c.930G>A) pathogenic?

ARSI p.Pro310= (c.930G>A) is classified Likely benign in ARSI (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-11). Rare (popmax 0.115%, nfe); Associated with Spastic paraplegia.

What condition is associated with ARSI p.Pro310= (c.930G>A)?

ARSI p.Pro310= (c.930G>A) is associated with Spastic paraplegia (ClinVar).

How common is ARSI p.Pro310= (c.930G>A) in the general population?

ARSI p.Pro310= (c.930G>A) is rare (popmax 0.115%, nfe) (gnomAD).

ARSI p.Pro310=

c.930G>A · rs140546154 · VCV703924

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, 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 -20	GERP -3.4
Overall
CADD	0.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% European (non-Finnish) · 1,358/1,179,858 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0943% 1,521/1,612,438 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.115%	869
Finnishnot grpmax-eligible	0.0989%	1,011
Remaining individualsnot grpmax-eligible	0.088%	1,136
Admixed American	0.0367%	2,726
African / African-American	0.028%	3,570
South Asian	0.00329%	30,349

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.Pro310=
Coding: c.930G>A
MANE Select: NM_001012301
dbSNP: rs140546154
Type: single nucleotide variant
Location: chr5:150297994 (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-pro310 (accessed [today's date]).

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