Is ARSI p.Ala29= (c.87C>T) pathogenic?

ARSI p.Ala29= (c.87C>T) is classified Benign/Likely benign in ARSI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Rare (popmax 0.644%, amr); Associated with Spastic paraplegia.

What condition is associated with ARSI p.Ala29= (c.87C>T)?

ARSI p.Ala29= (c.87C>T) is associated with Spastic paraplegia (ClinVar).

How common is ARSI p.Ala29= (c.87C>T) in the general population?

ARSI p.Ala29= (c.87C>T) is rare (popmax 0.644%, amr) (gnomAD).

ARSI p.Ala29=

c.87C>T · rs200012526 · VCV465198

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.644%, amr)

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 -0.47	GERP -5.2, phastCons 0.001
Overall
CADD	7.853	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.644% Admixed American · 377/58,550 alleles

Filtering AF 0.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.569%

Overall 0.439% 7,048/1,604,888 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.644%	155
European (non-Finnish)	0.533%	187
Remaining individualsnot grpmax-eligible	0.325%	307
Amishnot grpmax-eligible	0.219%	456
African / African-American	0.214%	468
Finnishnot grpmax-eligible	0.0434%	2,302
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,751

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.Ala29=
Coding: c.87C>T
MANE Select: NM_001012301
dbSNP: rs200012526
Type: single nucleotide variant
Location: chr5:150302287 (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-ala29 (accessed [today's date]).

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