Is SI p.Phe213= (c.639T>C) pathogenic?

SI p.Phe213= (c.639T>C) is classified Conflicting classifications of pathogenicity in SI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.0157%, nfe); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Phe213= (c.639T>C)?

SI p.Phe213= (c.639T>C) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Phe213= (c.639T>C) in the general population?

SI p.Phe213= (c.639T>C) is ultra-rare (popmax 0.0157%, 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.Phe213=

c.639T>C · rs368517998 · VCV344066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP -0.96, phastCons 1
Overall
CADD	10.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% European (non-Finnish) · 165/1,051,822 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0123% 177/1,439,866 alleles · ultra-rare exomes 159/1,296,862 · genomes 18/143,004 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0157%	6,375
Remaining individualsnot grpmax-eligible	0.0108%	9,275
African / African-American	0.00859%	11,637

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.Phe213=
Coding: c.639T>C
MANE Select: NM_001041
dbSNP: rs368517998
Type: single nucleotide variant
Location: chr3:165065429 (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 213: 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-phe213 (accessed [today's date]).

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