Is SOS2 p.Arg550= (c.1648C>A) pathogenic?

SOS2 p.Arg550= (c.1648C>A) is classified Likely benign in SOS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-12). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with SOS2 p.Arg550= (c.1648C>A)?

SOS2 p.Arg550= (c.1648C>A) is associated with Cardiovascular phenotype, Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Arg550= (c.1648C>A) in the general population?

SOS2 p.Arg550= (c.1648C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

SOS2 p.Arg550=

c.1648C>A · rs1344304906 · VCV1545955

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.4	GERP -2.3, phastCons 1
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,002 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,380 alleles · very rare exomes 3/1,461,208 · genomes 0/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,002
European (non-Finnish)	0.00017%	589,751

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: SOS2
Protein: p.Arg550=
Coding: c.1648C>A
MANE Select: NM_006939
dbSNP: rs1344304906
Type: single nucleotide variant
Location: chr14:50159635 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Noonan syndrome 9

Similar variants

SOS2 p.Arg550Leu Likely pathogenic ★ ⚠ same residue
SOS2 p.Arg550Gln Uncertain significance ★ ⚠ same residue
SOS2 p.Arg550Gly Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg550 (accessed [today's date]).

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