Is SOS2 p.Pro36Ala (c.106C>G) pathogenic?

SOS2 p.Pro36Ala (c.106C>G) is classified Uncertain significance in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-16). AlphaMissense: ambiguous (0.5196); Absent from gnomAD v4.1; Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Pro36Ala (c.106C>G)?

SOS2 p.Pro36Ala (c.106C>G) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Pro36Ala (c.106C>G) in the general population?

SOS2 p.Pro36Ala (c.106C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOS2 p.Pro36Ala (c.106C>G)?

AlphaMissense predicts ambiguous (score 0.5196) — an in-silico prediction, not a clinical call.

SOS2 p.Pro36Ala

c.106C>G · rs2503209915 · VCV2906579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5196 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,096)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Noonan syndrome 9

Computational evidence

Protein change
AlphaMissense	0.5196	ambiguous
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -12.77	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 72 kb · p 2.7e-07 · regional, not allelic
Overall
CADD	26.2	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

No allele count reported in gnomAD v4.1 (AN 1,576,096). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SOS2
Protein: p.Pro36Ala
Coding: c.106C>G
MANE Select: NM_006939
dbSNP: rs2503209915
Type: single nucleotide variant
Location: chr14:50204391 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB

Full SOS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Noonan syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SOS2 p.Pro36Leu Uncertain significance ★ ⚠ same residue
SOS2 p.Met267Lys Likely pathogenic ★★★ ⚠ same condition
SOS2 p.Ala1195Val Uncertain significance ★★★ ⚠ same condition
SOS2 p.Arg225Gln Uncertain significance ★★★ ⚠ same condition
SOS2 p.Arg986Lys Uncertain significance ★★★ ⚠ same condition
SOS2 p.Thr1079Ala Uncertain significance ★★★ ⚠ same condition
SOS2 p.Asn867Ser Likely benign ★★★ same condition
SOS2 p.Met267Arg Pathogenic/Likely pathogenic ★★ ⚠ 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/sos2-p-pro36ala (accessed [today's date]).

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