Is SON p.Pro570Ala (c.1708C>G) pathogenic?

SON p.Pro570Ala (c.1708C>G) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-07). AlphaMissense: likely benign (0.1136); Very rare (popmax 0.00196%, nfe).

How common is SON p.Pro570Ala (c.1708C>G) in the general population?

SON p.Pro570Ala (c.1708C>G) is very rare (popmax 0.00196%, nfe) (gnomAD).

What do computational predictors say about SON p.Pro570Ala (c.1708C>G)?

AlphaMissense predicts likely benign (score 0.1136) — an in-silico prediction, not a clinical call.

SON p.Pro570Ala

c.1708C>G · rs760968345 · VCV2179926

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1136	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP 4.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	21.6	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 0.00196% European (non-Finnish) · 23/1,174,424 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00149% 24/1,606,448 alleles · very rare exomes 20/1,454,506 · genomes 4/151,942 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00196%	51,062
African / African-American	0.00134%	74,680

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.Pro570Ala
Coding: c.1708C>G
MANE Select: NM_138927
dbSNP: rs760968345
Type: single nucleotide variant
Location: chr21:33550939 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB

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

Similar variants

SON p.Pro570= Likely benign ★★ same residue
SON p.Pro570Ser Uncertain significance ★ ⚠ same residue
SON p.Pro570fs Pathogenic ★ 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-pro570ala (accessed [today's date]).

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