Is SI p.Phe292= (c.876C>T) pathogenic?

SI p.Phe292= (c.876C>T) is classified Likely benign in SI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-21). Rare (popmax 0.186%, afr); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Phe292= (c.876C>T)?

SI p.Phe292= (c.876C>T) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Phe292= (c.876C>T) in the general population?

SI p.Phe292= (c.876C>T) is rare (popmax 0.186%, 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.Phe292=

c.876C>T · rs139642816 · VCV1621810

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.186%, 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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP -2.6, phastCons 1
Overall
CADD	8.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.186% African / African-American · 136/73,184 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.151%

Overall 0.0124% 192/1,546,678 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.186%	538
Remaining individualsnot grpmax-eligible	0.0233%	4,285
Middle Eastern	0.0169%	5,910
Admixed American	0.0169%	5,914
East Asian	0.00457%	21,887
South Asian	0.00341%	29,306
European (non-Finnish)	0.00231%	43,221

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.Phe292=
Coding: c.876C>T
MANE Select: NM_001041
dbSNP: rs139642816
Type: single nucleotide variant
Location: chr3:165063473 (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 292: 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 p.Phe292Leu 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-phe292 (accessed [today's date]).

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