Is SON p.Ala388Val (c.1163C>T) pathogenic?

SON p.Ala388Val (c.1163C>T) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-12). AlphaMissense: likely benign (0.1181); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with SON p.Ala388Val (c.1163C>T)?

SON p.Ala388Val (c.1163C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SON p.Ala388Val (c.1163C>T) in the general population?

SON p.Ala388Val (c.1163C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about SON p.Ala388Val (c.1163C>T)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

SON p.Ala388Val

c.1163C>T · VCV4831372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.99	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 5.9	GERP 3.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	24.1	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 0.00446% East Asian · 2/44,864 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00112% 18/1,613,940 alleles · very rare exomes 16/1,461,742 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,432
African / African-American	0.00267%	37,501
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,078
European (non-Finnish)	0.000932%	107,272

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.Ala388Val
Coding: c.1163C>T
MANE Select: NM_138927
Type: single nucleotide variant
Location: chr21:33550394 (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.Ala388= Likely 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-ala388val (accessed [today's date]).

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