Is SON p.Arg1965= (c.5895C>T) pathogenic?

SON p.Arg1965= (c.5895C>T) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-02). Very rare (popmax 0.00436%, afr).

How common is SON p.Arg1965= (c.5895C>T) in the general population?

SON p.Arg1965= (c.5895C>T) is very rare (popmax 0.00436%, afr) (gnomAD).

SON p.Arg1965=

c.5895C>T · rs898399292 · VCV743136

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00436%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -1.6
Overall
CADD	0.915	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00436% African / African-American · 3/68,874 alleles

Filtering AF 0.00116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000621%

Overall 0.000202% 3/1,484,654 alleles · very rare exomes 0/1,335,214 · genomes 3/149,440 · 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.Arg1965=
Coding: c.5895C>T
MANE Select: NM_138927
dbSNP: rs898399292
Type: single nucleotide variant
Location: chr21:33555126 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 1965: the 'disordered' region; the '7 x 7 aa repeats of p-s-r-r-s-r-[ts]' region; the '2 x 19 aa repeats of p-s-r-r-r-r-s-r-s-v-v-r-r-r-s-f-s-i-s' region

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

Similar variants

SON p.Arg1965His Conflicting classifications of pathogenicity ★ ⚠ same residue
SON p.Arg1965Cys Benign ★ ⚠ same residue
SON p.Arg1965_Thr1987del 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

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-arg1965 (accessed [today's date]).

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