Is ARSI p.Ser307= (c.921C>T) pathogenic?

ARSI p.Ser307= (c.921C>T) is classified Benign in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). Low-frequency (popmax 2.45%, sas); Associated with Spastic paraplegia.

What condition is associated with ARSI p.Ser307= (c.921C>T)?

ARSI p.Ser307= (c.921C>T) is associated with Spastic paraplegia (ClinVar).

How common is ARSI p.Ser307= (c.921C>T) in the general population?

ARSI p.Ser307= (c.921C>T) is low-frequency (popmax 2.45%, sas) (gnomAD).

ARSI p.Ser307=

c.921C>T · rs200155745 · VCV771626

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.45%, sas)

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 4.5	GERP -0.48, phastCons 1
Overall
CADD	6.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.45% South Asian · 2,232/91,074 alleles

Filtering AF 2.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.33%

Overall 0.145% 2,334/1,612,580 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.45%	41
Remaining individualsnot grpmax-eligible	0.139%	718
Middle Eastern	0.132%	758
African / African-American	0.00533%	18,760
East Asian	0.00223%	44,878
European (non-Finnish)	0.000169%	589,988

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.Ser307=
Coding: c.921C>T
MANE Select: NM_001012301
dbSNP: rs200155745
Type: single nucleotide variant
Location: chr5:150298003 (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.Ser307Asn 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
ARSI p.Ala78Thr 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-ser307 (accessed [today's date]).

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