Is ARSI p.Ala41= (c.123C>T) pathogenic?

ARSI p.Ala41= (c.123C>T) is classified Likely benign in ARSI (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-09). Very rare (popmax 8.48e-05%, nfe); Associated with ARSI-related disorder.

What condition is associated with ARSI p.Ala41= (c.123C>T)?

ARSI p.Ala41= (c.123C>T) is associated with ARSI-related disorder (ClinVar).

How common is ARSI p.Ala41= (c.123C>T) in the general population?

ARSI p.Ala41= (c.123C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ARSI p.Ala41=

c.123C>T · rs2532427971 · VCV3050253

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

ARSI-related disorder

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 -5.5	GERP -4.9
Overall
CADD	2.592	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,408 alleles

Overall 6.85e-05% 1/1,459,310 alleles · very rare

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.Ala41=
Coding: c.123C>T
MANE Select: NM_001012301
dbSNP: rs2532427971
Type: single nucleotide variant
Location: chr5:150302251 (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

ARSI-related disorder

Similar variants

ARSI p.Ala216Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala259Val Uncertain significance ★★ ⚠ same type
ARSI p.Ala264Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala399Asp Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Ser Uncertain significance ★★ ⚠ same type
ARSI p.Ala414Thr Uncertain significance ★★ ⚠ same type
ARSI p.Ala78Thr Uncertain significance ★★ ⚠ same type
ARSI p.Arg117Cys Uncertain significance ★★ ⚠ same type

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-ala41 (accessed [today's date]).

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