Is SON p.Ala336Val (c.1007C>T) pathogenic?

SON p.Ala336Val (c.1007C>T) is classified Benign/Likely benign in SON (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0729); Rare (popmax 0.541%, afr).

How common is SON p.Ala336Val (c.1007C>T) in the general population?

SON p.Ala336Val (c.1007C>T) is rare (popmax 0.541%, afr) (gnomAD).

What do computational predictors say about SON p.Ala336Val (c.1007C>T)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

SON p.Ala336Val

c.1007C>T · rs149343017 · VCV714903

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.541%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.20	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 -0.087	GERP -3.1, phastCons 0.64
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	12.09	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 0.541% African / African-American · 406/75,060 alleles

Filtering AF 0.497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.48%

Overall 0.0344% 555/1,614,246 alleles · rare exomes 333/1,461,884 · genomes 222/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.541%	185
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.035%	2,859
European (non-Finnish)	0.00754%	13,259
South Asian	0.00659%	15,181
East Asian	0.00223%	44,892

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.Ala336Val
Coding: c.1007C>T
MANE Select: NM_138927
dbSNP: rs149343017
Type: single nucleotide variant
Location: chr21:33550238 (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 p.Ala336= Likely benign ★★ same residue
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

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-ala336val (accessed [today's date]).

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