Is SI p.Arg692= (c.2076C>G) pathogenic?

SI p.Arg692= (c.2076C>G) is classified Likely benign in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). Very rare (popmax 0.00334%, amr).

How common is SI p.Arg692= (c.2076C>G) in the general population?

SI p.Arg692= (c.2076C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

SI p.Arg692=

c.2076C>G · rs1712802083 · VCV1388857

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -1.4, phastCons 0.94
Overall
CADD	0.959	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,906 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,612,414 alleles · very rare exomes 3/1,460,294 · genomes 0/152,120 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,953
African / African-American	0.00133%	74,930

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.Arg692=
Coding: c.2076C>G
MANE Select: NM_001041
dbSNP: rs1712802083
Type: single nucleotide variant
Location: chr3:165041023 (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 692: the 'isomaltase' region; an α-helix

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

Similar variants

SI p.Arg692Cys Uncertain significance ★★ ⚠ same residue
SI p.Arg692His Uncertain significance ★ ⚠ same residue
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

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-arg692 (accessed [today's date]).

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