Is SI p.Glu179Ter (c.535G>T) pathogenic?

SI p.Glu179Ter (c.535G>T) is classified Pathogenic in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-18). Very rare (popmax 0.00832%, nfe).

How common is SI p.Glu179Ter (c.535G>T) in the general population?

SI p.Glu179Ter (c.535G>T) is very rare (popmax 0.00832%, nfe) (gnomAD).

SI p.Glu179Ter

c.535G>T · rs1231349140 · VCV2417503

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00832%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 48
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -2.1
Overall
CADD	33.0	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 0.00832% European (non-Finnish) · 98/1,178,106 alleles

Filtering AF 0.00698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.00614% 99/1,611,586 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00832%	12,021
Remaining individualsnot grpmax-eligible	0.0016%	62,368

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: SI
Protein: p.Glu179Ter
Coding: c.535G>T
MANE Select: NM_001041
dbSNP: rs1231349140
Type: single nucleotide variant
Location: chr3:165067440 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB
Residue 179: the 'isomaltase' region

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

Similar variants

SI c.2426+1G>A Likely pathogenic ★★ same type
SI c.2737-2A>G Likely pathogenic ★★ same type
SI c.2893-1G>A Likely pathogenic ★★ same type
SI c.3099+1G>C Likely pathogenic ★★ same type
SI c.3521-1G>T Likely pathogenic ★★ same type
SI c.373+1G>A Likely pathogenic ★★ same type
SI c.4575+2T>C Likely pathogenic ★★ same type
SI c.4927-1G>A Likely pathogenic ★★ 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/si-p-glu179ter (accessed [today's date]).

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