Is SI p.Arg647fs (c.1940del) pathogenic?

SI p.Arg647fs (c.1940del) is classified Pathogenic in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-02). No gnomAD frequency available for this variant.

How common is SI p.Arg647fs (c.1940del) in the general population?

SI p.Arg647fs (c.1940del) is no gnomAD frequency available for this variant (gnomAD).

SI p.Arg647fs

c.1940del · rs2108222774 · VCV1457223

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.037	GERP 0.69, phastCons 0.94

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SI
Protein: p.Arg647fs
Coding: c.1940del
MANE Select: NM_001041
dbSNP: rs2108222774
Type: Deletion
Location: chr3:165043123 (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 647: the 'isomaltase' region; an α-helix

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

Similar variants

SI p.Arg647= Likely benign ★ same residue
SI p.Asn1403fs Pathogenic/Likely pathogenic ★★ same type
SI p.Gln278fs Pathogenic/Likely pathogenic ★★ same type
SI p.Leu1062_Tyr1063insTer Pathogenic/Likely pathogenic ★★ same type
SI p.Phe295_Leu296insTer Pathogenic/Likely pathogenic ★★ same type
SI p.Val342fs Pathogenic/Likely pathogenic ★★ same type
SI c.2737-11del Benign/Likely benign ★★ same type
SI c.2737-12_2737-11del Benign/Likely benign ★★ 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-arg647fs (accessed [today's date]).

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