Is SI p.Ile204Val (c.610A>G) pathogenic?

SI p.Ile204Val (c.610A>G) is classified Uncertain significance in SI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-15). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0267%, amr); Associated with Inborn genetic diseases.

What condition is associated with SI p.Ile204Val (c.610A>G)?

SI p.Ile204Val (c.610A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SI p.Ile204Val (c.610A>G) in the general population?

SI p.Ile204Val (c.610A>G) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about SI p.Ile204Val (c.610A>G)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

SI p.Ile204Val

c.610A>G · rs566771130 · VCV2200272

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.9
Regional constraint	o/e 1.10	unconstrained · MANE · 97 kb · p 9.1e-07 · regional, not allelic
Overall
CADD	1.001	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0267% Admixed American · 16/59,966 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0013% 21/1,610,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,748
Remaining individualsnot grpmax-eligible	0.00642%	15,586
European (non-Finnish)	8.49e-05%	1,177,862

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.Ile204Val
Coding: c.610A>G
MANE Select: NM_001041
dbSNP: rs566771130
Type: single nucleotide variant
Location: chr3:165067365 (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 204: 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.Ile204Thr Uncertain significance ★★ ⚠ same residue
SI p.Ile204Phe 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-ile204val (accessed [today's date]).

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