Is SOS2 p.Ser192Arg (c.574A>C) pathogenic?

SOS2 p.Ser192Arg (c.574A>C) is classified Uncertain significance in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: ambiguous (0.4539); Absent from gnomAD v4.1; Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Ser192Arg (c.574A>C)?

SOS2 p.Ser192Arg (c.574A>C) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Ser192Arg (c.574A>C) in the general population?

SOS2 p.Ser192Arg (c.574A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOS2 p.Ser192Arg (c.574A>C)?

AlphaMissense predicts ambiguous (score 0.4539) — an in-silico prediction, not a clinical call.

SOS2 p.Ser192Arg

c.574A>C · rs1886005265 · VCV1480438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Noonan syndrome 9

Computational evidence

Protein change
AlphaMissense	0.4539	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -7.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -5.3, phastCons 0.81
Regional constraint	o/e 0.81	unconstrained · MANE · 72 kb · p 2.7e-07 · regional, not allelic
Overall
CADD	19.61	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SOS2
Protein: p.Ser192Arg
Coding: c.574A>C
MANE Select: NM_006939
dbSNP: rs1886005265
Type: single nucleotide variant
Location: chr14:50188637 (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.Ser192Thr Uncertain significance ★★ ⚠ same residue
SOS2 p.Ser192Gly 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

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-ser192arg (accessed [today's date]).

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