Is SI p.Ala714fs (c.2141del) pathogenic?

SI p.Ala714fs (c.2141del) is classified Pathogenic in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). Very rare (popmax 8.49e-05%, nfe).

How common is SI p.Ala714fs (c.2141del) in the general population?

SI p.Ala714fs (c.2141del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

SI p.Ala714fs

c.2141del · rs2473351517 · VCV2818747

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

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 18 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2	GERP -3.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,794 alleles

Overall 6.21e-05% 1/1,611,274 alleles · very rare exomes 1/1,459,028 · genomes 0/152,246 · joint denominator

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.Ala714fs
Coding: c.2141del
MANE Select: NM_001041
dbSNP: rs2473351517
Type: Deletion
Location: chr3:165040958 (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 714: the 'isomaltase' region; a β-strand

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

Similar variants

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
SI c.2737-17_2737-11del 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-ala714fs (accessed [today's date]).

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