Is SON p.Arg1864Pro (c.5591G>C) pathogenic?

SON p.Arg1864Pro (c.5591G>C) is classified Uncertain significance in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely pathogenic (0.8434); Ultra-rare (popmax 0.0267%, eas).

How common is SON p.Arg1864Pro (c.5591G>C) in the general population?

SON p.Arg1864Pro (c.5591G>C) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about SON p.Arg1864Pro (c.5591G>C)?

AlphaMissense predicts likely pathogenic (score 0.8434) — an in-silico prediction, not a clinical call.

SON p.Arg1864Pro

c.5591G>C · rs776976656 · VCV1940072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8434	likely pathogenic
REVEL	0.182	moderately benign-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 2,223 bp · p 0.00022 · regional, not allelic
Overall
CADD	24.7	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 0.0267% East Asian · 12/44,880 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000744% 12/1,613,946 alleles · ultra-rare exomes 12/1,461,718 · genomes 0/152,228 · 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.Arg1864Pro
Coding: c.5591G>C
MANE Select: NM_138927
dbSNP: rs776976656
Type: single nucleotide variant
Location: chr21:33554822 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 1864: the 'disordered' region

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

Similar variants

SON p.Arg1864Gly Uncertain significance ★ ⚠ same residue
SON p.Arg1864Trp Uncertain significance ★ ⚠ same residue
SON p.Arg1864Gln 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

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-arg1864pro (accessed [today's date]).

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