Is SON p.Ala941Val (c.2822C>T) pathogenic?

SON p.Ala941Val (c.2822C>T) is classified Uncertain significance in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-16). AlphaMissense: likely pathogenic (0.614); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with SON p.Ala941Val (c.2822C>T)?

SON p.Ala941Val (c.2822C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SON p.Ala941Val (c.2822C>T) in the general population?

SON p.Ala941Val (c.2822C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about SON p.Ala941Val (c.2822C>T)?

AlphaMissense predicts likely pathogenic (score 0.614) — an in-silico prediction, not a clinical call.

SON p.Ala941Val

c.2822C>T · rs763756683 · VCV2212470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.614 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.614	likely pathogenic
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 968 bp · p 9.6e-05 · regional, not allelic
Overall
CADD	26.1	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000496% 8/1,614,078 alleles · ultra-rare exomes 8/1,461,880 · genomes 0/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.00439%	22,771
Remaining individualsnot grpmax-eligible	0.0032%	31,250

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.Ala941Val
Coding: c.2822C>T
MANE Select: NM_138927
dbSNP: rs763756683
Type: single nucleotide variant
Location: chr21:33552053 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 941: 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

Disease context

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

Similar variants

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
SON p.Ala1309Gly 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-ala941val (accessed [today's date]).

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