Is SON p.Glu1393= (c.4179G>A) pathogenic?

SON p.Glu1393= (c.4179G>A) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). Absent from gnomAD v4.1.

How common is SON p.Glu1393= (c.4179G>A) in the general population?

SON p.Glu1393= (c.4179G>A) is absent from gnomAD v4.1 (gnomAD).

SON p.Glu1393=

c.4179G>A · rs769227177 · VCV2768829

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.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.55	GERP 0.4
Overall
CADD	0.904	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: SON
Protein: p.Glu1393=
Coding: c.4179G>A
MANE Select: NM_138927
dbSNP: rs769227177
Type: single nucleotide variant
Location: chr21:33553410 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB

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

Similar variants

SON p.Glu1393Asp Uncertain significance ★ ⚠ same residue
SON c.6321+1G>A Pathogenic ★★ same type
SON p.Arg1081Ter Pathogenic ★★ same type
SON p.Arg1112Ter Pathogenic ★★ same type
SON p.Arg1825Ter Pathogenic ★★ same type
SON p.Arg2008Ter Pathogenic ★★ same type
SON p.Gln96Ter Pathogenic/Likely pathogenic ★★ same type
SON c.6657+160A>C 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/son-p-glu1393 (accessed [today's date]).

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