Is SON p.Ser799Asn (c.2396G>A) pathogenic?

SON p.Ser799Asn (c.2396G>A) is classified Uncertain significance in SON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-30). AlphaMissense: ambiguous (0.4417); Very rare (popmax 8.48e-05%, nfe).

How common is SON p.Ser799Asn (c.2396G>A) in the general population?

SON p.Ser799Asn (c.2396G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about SON p.Ser799Asn (c.2396G>A)?

AlphaMissense predicts ambiguous (score 0.4417) — an in-silico prediction, not a clinical call.

SON p.Ser799Asn

c.2396G>A · rs1212612604 · VCV1394701

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4417 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4417	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -11.50	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 4, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 210 bp · p 1.7e-08 · regional, not allelic
Overall
CADD	18.94	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,494 alleles

Overall 6.21e-05% 1/1,611,274 alleles · very rare exomes 1/1,459,576 · genomes 0/151,698 · 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: SON
Protein: p.Ser799Asn
Coding: c.2396G>A
MANE Select: NM_138927
dbSNP: rs1212612604
Type: single nucleotide variant
Location: chr21:33551627 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 799: the '17 x 10 aa tandem repeats of l-a-[st]-[nsg]-[ts]-mdsqm' region

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

Similar variants

SON p.Ser799= Benign/Likely benign ★★ 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-ser799asn (accessed [today's date]).

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