Is SI p.Cys283Phe (c.848G>T) pathogenic?

SI p.Cys283Phe (c.848G>T) is classified Uncertain significance in SI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.6696); Very rare (popmax 8.79e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SI p.Cys283Phe (c.848G>T)?

SI p.Cys283Phe (c.848G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SI p.Cys283Phe (c.848G>T) in the general population?

SI p.Cys283Phe (c.848G>T) is very rare (popmax 8.79e-05%, nfe) (gnomAD).

What do computational predictors say about SI p.Cys283Phe (c.848G>T)?

AlphaMissense predicts likely pathogenic (score 0.6696) — an in-silico prediction, not a clinical call.

SI p.Cys283Phe

c.848G>T · rs2473422091 · VCV3162047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.79e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6696	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -10.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.79e-05% European (non-Finnish) · 1/1,137,642 alleles

Overall 6.41e-05% 1/1,560,160 alleles · very rare exomes 1/1,408,718 · genomes 0/151,442 · joint denominator

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.Cys283Phe
Coding: c.848G>T
MANE Select: NM_001041
dbSNP: rs2473422091
Type: single nucleotide variant
Location: chr3:165063501 (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 283: the 'isomaltase' region; a β-strand

Full SI gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SI p.Cys283Ser Uncertain significance ★ ⚠ same residue
SI p.Cys283Tyr Uncertain significance ★ ⚠ same residue
SI p.Ala1654Asp Uncertain significance ★★ ⚠ same condition
SI p.Ala429Thr Uncertain significance ★★ ⚠ same condition
SI p.Ala573Val Uncertain significance ★★ ⚠ same condition
SI p.Ala760Val Uncertain significance ★★ ⚠ same condition
SI p.Ala808Thr Uncertain significance ★★ ⚠ same condition
SI p.Ala826Asp Uncertain significance ★★ ⚠ 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-cys283phe (accessed [today's date]).

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