Is SI p.Gln151Arg (c.452A>G) pathogenic?

SI p.Gln151Arg (c.452A>G) is classified Uncertain significance in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.1514); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SI p.Gln151Arg (c.452A>G)?

SI p.Gln151Arg (c.452A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SI p.Gln151Arg (c.452A>G) in the general population?

SI p.Gln151Arg (c.452A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about SI p.Gln151Arg (c.452A>G)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

SI p.Gln151Arg

c.452A>G · VCV3441718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,748 alleles

Overall 6.84e-05% 1/1,461,548 alleles · very rare

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.Gln151Arg
Coding: c.452A>G
MANE Select: NM_001041
Type: single nucleotide variant
Location: chr3:165068753 (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 151: the 'isomaltase' region; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SI p.Gln151= Conflicting classifications of pathogenicity ★ same residue
SI p.Ala1654Asp Uncertain significance ★★ ⚠ same condition
SI p.Ala429Thr Uncertain significance ★★ ⚠ same condition
SI p.Ala573Val Uncertain significance ★★ ⚠ same condition
SI p.Ala760Val Uncertain significance ★★ ⚠ same condition
SI p.Ala808Thr Uncertain significance ★★ ⚠ same condition
SI p.Ala826Asp Uncertain significance ★★ ⚠ same condition
SI p.Arg1078Gln Uncertain significance ★★ same condition

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-gln151arg (accessed [today's date]).

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