Is ARGLU1 p.Ter274= (c.822A>G) pathogenic?

ARGLU1 p.Ter274= (c.822A>G) is classified Likely benign in ARGLU1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-12). Ultra-rare (popmax 0.0966%, afr); Associated with ARGLU1-related disorder.

What condition is associated with ARGLU1 p.Ter274= (c.822A>G)?

ARGLU1 p.Ter274= (c.822A>G) is associated with ARGLU1-related disorder (ClinVar).

How common is ARGLU1 p.Ter274= (c.822A>G) in the general population?

ARGLU1 p.Ter274= (c.822A>G) is ultra-rare (popmax 0.0966%, afr) (gnomAD).

ARGLU1 p.Ter274=

c.822A>G · rs200630944 · VCV3034677

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0966%, afr)

Conditions

ARGLU1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a LoF-intolerant gene
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.66, phastCons 1
Overall
CADD	11.42	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0966% African / African-American · 70/72,500 alleles

Filtering AF 0.0784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0717%

Overall 0.00922% 146/1,582,790 alleles · ultra-rare exomes 91/1,430,570 · genomes 55/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0966%	1,036
Middle Eastern	0.0341%	2,931
Remaining individualsnot grpmax-eligible	0.0147%	6,803
Admixed American	0.00573%	17,449
European (non-Finnish)	0.00521%	19,189
South Asian	0.0012%	83,410

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: ARGLU1
Protein: p.Ter274=
Coding: c.822A>G
MANE Select: NM_018011
dbSNP: rs200630944
Type: single nucleotide variant
Location: chr13:106543996 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.25

Full ARGLU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARGLU1-related disorder

Similar variants

ARGLU1 p.Ala186Thr Benign same condition
ARGLU1 p.Lys16= Likely benign same condition
ARGLU1 p.Arg155Gln Uncertain significance ★ ⚠ same type
ARGLU1 p.Arg159Gln Uncertain significance ★ ⚠ same type
ARGLU1 p.Arg195His Uncertain significance ★ ⚠ same type
ARGLU1 p.Asp33Glu Uncertain significance ★ ⚠ same type
ARGLU1 p.Asp71Glu Uncertain significance ★ ⚠ same type
ARGLU1 p.Gln187Arg 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/arglu1-p-ter274 (accessed [today's date]).

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