Is SON p.Ala369Val (c.1106C>T) pathogenic?

SON p.Ala369Val (c.1106C>T) is classified Conflicting classifications of pathogenicity in SON (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-05-22). AlphaMissense: likely benign (0.0874); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with SON p.Ala369Val (c.1106C>T)?

SON p.Ala369Val (c.1106C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SON p.Ala369Val (c.1106C>T) in the general population?

SON p.Ala369Val (c.1106C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about SON p.Ala369Val (c.1106C>T)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

SON p.Ala369Val

c.1106C>T · rs540447388 · VCV2919798

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 4.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	23.1	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 0.0107% African / African-American · 8/75,052 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00551% 89/1,614,136 alleles · ultra-rare exomes 77/1,461,830 · genomes 12/152,306 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
African / African-Americangrpmax	0.0107%	9,381
South Asian	0.00988%	10,121
Remaining individualsnot grpmax-eligible	0.008%	12,501
East Asian	0.00446%	22,441
European (non-Finnish)	0.00415%	24,082

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala369Val
Coding: c.1106C>T
MANE Select: NM_138927
dbSNP: rs540447388
Type: single nucleotide variant
Location: chr21:33550337 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SON p.Ala369= Benign ★ same residue
SON p.Arg1112Ter Pathogenic ★★ same condition
SON p.Arg1031Cys Uncertain significance ★★ ⚠ same condition
SON p.Arg1993Cys Uncertain significance ★★ ⚠ same condition
SON p.Gly47Asp Uncertain significance ★★ ⚠ same condition
SON p.Ser1437Cys Uncertain significance ★★ ⚠ same condition
SON p.Thr1156Lys Uncertain significance ★★ ⚠ same condition
SON p.Ala1109Val Likely benign ★★ same condition

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-ala369val (accessed [today's date]).

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