Is SON p.Asp940Val (c.2819A>T) pathogenic?

SON p.Asp940Val (c.2819A>T) is classified Uncertain significance in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.9776); Absent from gnomAD v4.1.

How common is SON p.Asp940Val (c.2819A>T) in the general population?

SON p.Asp940Val (c.2819A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SON p.Asp940Val (c.2819A>T)?

AlphaMissense predicts likely pathogenic (score 0.9776) — an in-silico prediction, not a clinical call.

SON p.Asp940Val

c.2819A>T · rs775303990 · VCV2504448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9776 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9776	likely pathogenic · top 9% in SON
REVEL	0.135	moderately benign-leaning
SaProt	LLR -12.53	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 4.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 968 bp · p 9.6e-05 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SON
Protein: p.Asp940Val
Coding: c.2819A>T
MANE Select: NM_138927
dbSNP: rs775303990
Type: single nucleotide variant
Location: chr21:33552050 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 940: the '11 x 7 aa tandem repeats of [dr]-p-y-r-[li][ag][qhp]' 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-asp940val (accessed [today's date]).

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