Is SON p.Ala496= (c.1488G>A) pathogenic?

SON p.Ala496= (c.1488G>A) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). Ultra-rare (popmax 0.0439%, sas).

How common is SON p.Ala496= (c.1488G>A) in the general population?

SON p.Ala496= (c.1488G>A) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

SON p.Ala496=

c.1488G>A · rs771380863 · VCV2182126

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP 0.62, phastCons 1
Overall
CADD	15.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,088 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0057% 92/1,614,054 alleles · ultra-rare exomes 87/1,461,868 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.0039%	25,653
Admixed American	0.00333%	30,003
East Asian	0.00223%	44,900

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.Ala496=
Coding: c.1488G>A
MANE Select: NM_138927
dbSNP: rs771380863
Type: single nucleotide variant
Location: chr21:33550719 (GRCh38)

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

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-ala496 (accessed [today's date]).

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