Is SON p.Ala1723= (c.5169C>T) pathogenic?

SON p.Ala1723= (c.5169C>T) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-10). Very rare (popmax 0.00167%, amr).

How common is SON p.Ala1723= (c.5169C>T) in the general population?

SON p.Ala1723= (c.5169C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

SON p.Ala1723=

c.5169C>T · rs2085906718 · VCV2849773

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -3.7, phastCons 0.77
Overall
CADD	4.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,990 alleles

Overall 6.2e-05% 1/1,613,998 alleles · very rare exomes 0/1,461,882 · genomes 1/152,116 · 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.Ala1723=
Coding: c.5169C>T
MANE Select: NM_138927
dbSNP: rs2085906718
Type: single nucleotide variant
Location: chr21:33554400 (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 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-ala1723 (accessed [today's date]).

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