Is SI p.Tyr562= (c.1686T>C) pathogenic?

SI p.Tyr562= (c.1686T>C) is classified Likely benign in SI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). Ultra-rare (popmax 0.0105%, nfe); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Tyr562= (c.1686T>C)?

SI p.Tyr562= (c.1686T>C) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Tyr562= (c.1686T>C) in the general population?

SI p.Tyr562= (c.1686T>C) is ultra-rare (popmax 0.0105%, nfe) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI p.Tyr562=

c.1686T>C · rs763063946 · VCV1623823

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, nfe)

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.099	GERP -3.9, phastCons 0.056
Overall
CADD	4.188	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% European (non-Finnish) · 123/1,173,982 alleles

Filtering AF 0.00897% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0084%

Overall 0.00809% 130/1,607,234 alleles · ultra-rare exomes 117/1,455,042 · genomes 13/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0105%	9,545
Remaining individualsnot grpmax-eligible	0.00803%	12,452
Admixed American	0.00167%	59,952
South Asian	0.0011%	90,980

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.Tyr562=
Coding: c.1686T>C
MANE Select: NM_001041
dbSNP: rs763063946
Type: single nucleotide variant
Location: chr3:165049156 (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 562: the 'isomaltase' region; an α-helix

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 p.Tyr562Phe Uncertain significance ★ ⚠ same residue
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

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-tyr562 (accessed [today's date]).

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