Is ARSI p.Val267= (c.801G>A) pathogenic?

ARSI p.Val267= (c.801G>A) is classified Benign in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-25). Common (popmax 6.48%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Spastic paraplegia.

What condition is associated with ARSI p.Val267= (c.801G>A)?

ARSI p.Val267= (c.801G>A) is associated with Spastic paraplegia (ClinVar).

ARSI p.Val267=

Q: How common is ARSI p.Val267= (c.801G>A) in the general population?

ARSI p.Val267= (c.801G>A) is common (popmax 6.48%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.801G>A · rs114744538 · VCV533755

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.48%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.33	GERP -3.7, phastCons 0.089
Overall
CADD	5.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.48% African / African-American · 4,857/75,004 alleles

Filtering AF 6.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.26%

Overall 0.356% 5,753/1,613,776 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.48%	15
Admixed American	0.512%	195
Remaining individualsnot grpmax-eligible	0.474%	211
Middle Eastern	0.462%	216
Ashkenazi Jewishnot grpmax-eligible	0.199%	502
European (non-Finnish)	0.0166%	6,020
South Asian	0.00878%	11,384
Finnishnot grpmax-eligible	0.00314%	31,861

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.Val267=
Coding: c.801G>A
MANE Select: NM_001012301
dbSNP: rs114744538
Type: single nucleotide variant
Location: chr5:150298123 (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-val267 (accessed [today's date]).

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