Is SI p.Phe6Leu (c.16T>C) pathogenic?

SI p.Phe6Leu (c.16T>C) is classified Uncertain significance in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely pathogenic (0.5754); Absent from gnomAD v4.1; Associated with congenital sucrase-isomaltase deficiency.

What condition is associated with SI p.Phe6Leu (c.16T>C)?

SI p.Phe6Leu (c.16T>C) is associated with congenital sucrase-isomaltase deficiency (ClinVar).

How common is SI p.Phe6Leu (c.16T>C) in the general population?

SI p.Phe6Leu (c.16T>C) is absent from gnomAD v4.1 (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.Phe6Leu (c.16T>C)?

AlphaMissense predicts likely pathogenic (score 0.5754) — an in-silico prediction, not a clinical call.

SI p.Phe6Leu

c.16T>C · rs886058151 · VCV344076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital sucrase-isomaltase deficiency

Computational evidence

Protein change
AlphaMissense	0.5754	likely pathogenic
REVEL	0.498	indeterminate
SaProt	LLR -5.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SI
Protein: p.Phe6Leu
Coding: c.16T>C
MANE Select: NM_001041
dbSNP: rs886058151
Type: single nucleotide variant
Location: chr3:165075997 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.86 · 2 PDB

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.Phe6Cys Uncertain significance ★ same residue
SI p.Phe6Tyr 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

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-phe6leu (accessed [today's date]).

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