Is SI p.Leu502= (c.1506T>G) pathogenic?

SI p.Leu502= (c.1506T>G) is classified Benign/Likely benign in SI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Rare (popmax 0.527%, afr); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Leu502= (c.1506T>G)?

SI p.Leu502= (c.1506T>G) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Leu502= (c.1506T>G) in the general population?

SI p.Leu502= (c.1506T>G) is rare (popmax 0.527%, afr) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SI p.Leu502=

c.1506T>G · rs113511967 · VCV1170253

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.527%, afr)

Conditions

congenital sucrase-isomaltase deficiency

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 1	GERP -0.16, phastCons 0.99
Overall
CADD	9.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.527% African / African-American · 393/74,614 alleles

Filtering AF 0.484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.467%

Overall 0.0301% 479/1,590,642 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.527%	190
Remaining individualsnot grpmax-eligible	0.0599%	1,668
Admixed American	0.0568%	1,762
Middle Eastern	0.0501%	1,995
South Asian	0.00442%	22,649
European (non-Finnish)	0.00069%	144,904

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.Leu502=
Coding: c.1506T>G
MANE Select: NM_001041
dbSNP: rs113511967
Type: single nucleotide variant
Location: chr3:165055200 (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 502: the 'isomaltase' region; a β-strand

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

Disease context

congenital sucrase-isomaltase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital sucrase-isomaltase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SI c.2426+1G>A Likely pathogenic ★★ same condition
SI c.2893-1G>A Likely pathogenic ★★ same condition
SI c.3099+1G>C Likely pathogenic ★★ same condition
SI c.3521-1G>T Likely pathogenic ★★ same condition
SI c.373+1G>A Likely pathogenic ★★ same condition
SI c.4575+2T>C Likely pathogenic ★★ same condition
SI c.4927-1G>A Likely pathogenic ★★ same condition
SI c.5248-2A>C Likely pathogenic ★★ 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-leu502 (accessed [today's date]).

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