Is SON p.Glu512fs (c.1535_1536del) pathogenic?

SON p.Glu512fs (c.15351536del) is classified Pathogenic in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-02). No gnomAD frequency available for this variant.

How common is SON p.Glu512fs (c.1535_1536del) in the general population?

SON p.Glu512fs (c.1535_1536del) is no gnomAD frequency available for this variant (gnomAD).

SON p.Glu512fs

c.1535_1536del · rs1601260044 · VCV817767

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 4.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SON
Protein: p.Glu512fs
Coding: c.1535_1536del
MANE Select: NM_138927
dbSNP: rs1601260044
Type: Microsatellite
Location: chr21:33550764 (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.Gln874fs Pathogenic ★★ same type
SON p.Leu1593fs Pathogenic ★★ same type
SON p.1957SRTPSRR[3] Uncertain significance ★★ same type
SON c.6322-16_6322-13del Benign/Likely benign ★★ same type
SON p.1036AYERSMMS[1] Likely benign ★★ same type
SON p.1957SRTPSRR[4] Likely benign ★★ same type
SON p.224EQS[1] Likely benign ★★ same type
SON p.Arg1998_Arg1999insSerArgThrProSerArgArg Likely benign ★★ 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-glu512fs (accessed [today's date]).

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