Is SOS2 p.Pro237fs (c.710del) pathogenic?

SOS2 p.Pro237fs (c.710del) is classified Uncertain significance in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). No allele count reported in gnomAD v4.1 (AN 1,593,566); Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Pro237fs (c.710del)?

SOS2 p.Pro237fs (c.710del) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Pro237fs (c.710del) in the general population?

SOS2 p.Pro237fs (c.710del) is no allele count reported in gnomAD v4.1 (AN 1,593,566) (gnomAD).

SOS2 p.Pro237fs

c.710del · rs2139733738 · VCV1514208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,593,566)

Conditions

Noonan syndrome 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.3	GERP 0.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,593,566). 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.Pro237fs
Coding: c.710del
MANE Select: NM_006939
dbSNP: rs2139733738
Type: Deletion
Location: chr14:50188501 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB
Residue 237: the dh domain

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.Pro237Ser Uncertain significance ★ ⚠ same residue
SOS2 p.Ile1252del Benign ★★★ same condition
SOS2 c.1068+17_1068+18del Likely benign ★★ same condition
SOS2 c.2057+19_2057+20del Benign/Likely benign ★★ same condition
SOS2 c.2384+10_2384+13del Likely benign ★★ same condition
SOS2 c.2786-6del Benign/Likely benign ★★ same condition
SOS2 c.346-10_346-8del Likely benign ★★ same condition
SOS2 c.3490-4del Benign/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/sos2-p-pro237fs (accessed [today's date]).

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