Is SON p.Pro340Ser (c.1018C>T) pathogenic?

SON p.Pro340Ser (c.1018C>T) is classified Uncertain significance in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-28). AlphaMissense: likely benign (0.104); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with SON p.Pro340Ser (c.1018C>T)?

SON p.Pro340Ser (c.1018C>T) is associated with intellectual disability (ClinVar).

How common is SON p.Pro340Ser (c.1018C>T) in the general population?

SON p.Pro340Ser (c.1018C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SON p.Pro340Ser (c.1018C>T)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

SON p.Pro340Ser

c.1018C>T · VCV4074773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.68	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 3.3	GERP 4.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro340Ser
Coding: c.1018C>T
MANE Select: NM_138927
Type: single nucleotide variant
Location: chr21:33550249 (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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SON p.Met815Leu Benign/Likely benign ★★ ⚠ same condition
SON p.Asn1724Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
SON p.Gln2290Pro Uncertain significance ★ ⚠ same condition
SON p.Tyr1140His Uncertain significance ★ ⚠ same condition
SON p.Val1410Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
SON p.Arg1112fs Pathogenic ★ same condition
SON p.Ser1594fs Pathogenic ★ same condition
SON c.6321+1G>A 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-pro340ser (accessed [today's date]).

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