Is ARSI p.His194= (c.582C>T) pathogenic?

ARSI p.His194= (c.582C>T) is classified Likely benign in ARSI (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-27). Very rare (popmax 0.00446%, eas).

How common is ARSI p.His194= (c.582C>T) in the general population?

ARSI p.His194= (c.582C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

ARSI p.His194=

c.582C>T · rs762293058 · VCV726181

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -5.6	GERP -5.1
Overall
CADD	1.882	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000958% 14/1,461,792 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000932%	107,275

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.His194=
Coding: c.582C>T
MANE Select: NM_001012301
dbSNP: rs762293058
Type: single nucleotide variant
Location: chr5:150298342 (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

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-his194 (accessed [today's date]).

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