Is SI p.Phe1745Cys (c.5234T>G) pathogenic?

SI p.Phe1745Cys (c.5234T>G) is classified Conflicting classifications of pathogenicity in SI (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-04-13). AlphaMissense: likely pathogenic (0.8836); Rare (popmax 0.162%, nfe); Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Phe1745Cys (c.5234T>G)?

SI p.Phe1745Cys (c.5234T>G) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Phe1745Cys (c.5234T>G) in the general population?

SI p.Phe1745Cys (c.5234T>G) is rare (popmax 0.162%, nfe) (gnomAD).

How is Congenital sucrase-isomaltase deficiency inherited?

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

What do computational predictors say about SI p.Phe1745Cys (c.5234T>G)?

AlphaMissense predicts likely pathogenic (score 0.8836) — an in-silico prediction, not a clinical call.

SI p.Phe1745Cys

c.5234T>G · rs79717168 · VCV1417

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.8836 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.162%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
AlphaMissense	0.8836	likely pathogenic
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -15.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.162% European (non-Finnish) · 1,826/1,128,882 alleles

Filtering AF 0.156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.133% 2,066/1,548,244 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.241%	415
Remaining individualsnot grpmax-eligible	0.165%	605
European (non-Finnish)grpmax	0.162%	618
Admixed American	0.0482%	2,073
Finnishnot grpmax-eligible	0.0367%	2,728
African / African-American	0.0311%	3,213
Middle Eastern	0.0174%	5,750

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe1745Cys
Coding: c.5234T>G
MANE Select: NM_001041
dbSNP: rs79717168
Type: single nucleotide variant
Location: chr3:164983015 (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 1745: the 'sucrase' region; a UniProt-annotated variant site (in csid)

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-phe1745cys (accessed [today's date]).

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