Is SIAE p.Ile68= (c.204C>T) pathogenic?

SIAE p.Ile68= (c.204C>T) is classified Likely benign in SIAE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-27). Absent from gnomAD v4.1.

How common is SIAE p.Ile68= (c.204C>T) in the general population?

SIAE p.Ile68= (c.204C>T) is absent from gnomAD v4.1 (gnomAD).

SIAE p.Ile68=

c.204C>T · rs1317102366 · VCV2088453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP -0.76, phastCons 1
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

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: SIAE
Protein: p.Ile68=
Coding: c.204C>T
MANE Select: NM_170601
dbSNP: rs1317102366
Type: single nucleotide variant
Location: chr11:124669385 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.26

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

Similar variants

SIAE p.Ile68Val Uncertain significance ★ ⚠ same residue
SIAE p.Ala385Thr Uncertain significance ★★ ⚠ same type
SIAE p.Arg301His Uncertain significance ★★ ⚠ same type
SIAE p.Arg306Cys Uncertain significance ★★ ⚠ same type
SIAE p.Cys196Phe Uncertain significance ★★ ⚠ same type
SIAE p.Cys449Ser Uncertain significance ★★ ⚠ same type
SIAE p.Gln309Arg Uncertain significance ★★ ⚠ same type
SIAE p.Glu399Lys Uncertain significance ★★ ⚠ same type

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/siae-p-ile68 (accessed [today's date]).

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