Is SI p.Thr964= (c.2892G>A) pathogenic?

SI p.Thr964= (c.2892G>A) is classified Conflicting classifications of pathogenicity in SI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-24). Rare (popmax 0.417%, sas); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Thr964= (c.2892G>A)?

SI p.Thr964= (c.2892G>A) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Thr964= (c.2892G>A) in the general population?

SI p.Thr964= (c.2892G>A) is rare (popmax 0.417%, sas) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

SI p.Thr964=

c.2892G>A · rs145486890 · VCV344035

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.417%, sas)

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.86	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.64	loss · gain 0.22 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.36	GERP 0.85, phastCons 0.023
Overall
CADD	17.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.417% South Asian · 379/90,782 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.369%

Overall 0.0724% 1,164/1,607,308 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.417%	240
Middle Eastern	0.328%	305
Ashkenazi Jewishnot grpmax-eligible	0.0987%	1,013
Remaining individualsnot grpmax-eligible	0.0965%	1,036
Admixed American	0.0874%	1,145
European (non-Finnish)	0.052%	1,924
African / African-American	0.0134%	7,447
Finnishnot grpmax-eligible	0.00627%	15,960

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.Thr964=
Coding: c.2892G>A
MANE Select: NM_001041
dbSNP: rs145486890
Type: single nucleotide variant
Location: chr3:165030712 (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 964: the 'isomaltase' region; the p-type 2 domain

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.Thr964Met 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-thr964 (accessed [today's date]).

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