Is SON p.Ser843= (c.2529T>C) pathogenic?

SON p.Ser843= (c.2529T>C) is classified Likely benign in SON (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). Ultra-rare (popmax 0.0592%, sas).

How common is SON p.Ser843= (c.2529T>C) in the general population?

SON p.Ser843= (c.2529T>C) is ultra-rare (popmax 0.0592%, sas) (gnomAD).

SON p.Ser843=

c.2529T>C · rs1485206768 · VCV3051215

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0592%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -2.3
Overall
CADD	3.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0592% South Asian · 53/89,596 alleles

Filtering AF 0.0464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0419%

Overall 0.00565% 89/1,576,588 alleles · ultra-rare exomes 56/1,460,366 · genomes 33/116,222 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.181%	554
South Asiangrpmax	0.0592%	1,690
African / African-American	0.0127%	7,903
Admixed American	0.00875%	11,435
East Asian	0.00692%	14,447
Ashkenazi Jewishnot grpmax-eligible	0.00345%	28,970
Finnishnot grpmax-eligible	0.00164%	60,986
Remaining individualsnot grpmax-eligible	0.00162%	61,890
European (non-Finnish)	0.00137%	72,866

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser843=
Coding: c.2529T>C
MANE Select: NM_138927
dbSNP: rs1485206768
Type: single nucleotide variant
Location: chr21:33551760 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 843: 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 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
SON c.6657+316G>A 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-ser843 (accessed [today's date]).

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