Is SOS2 p.Pro799= (c.2397G>A) pathogenic?

SOS2 p.Pro799= (c.2397G>A) is classified Likely benign in SOS2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-27). Very rare (popmax 0.00344%, sas); Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Pro799= (c.2397G>A)?

SOS2 p.Pro799= (c.2397G>A) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Pro799= (c.2397G>A) in the general population?

SOS2 p.Pro799= (c.2397G>A) is very rare (popmax 0.00344%, sas) (gnomAD).

SOS2 p.Pro799=

c.2397G>A · rs770022419 · VCV1301363

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00344%, sas)

Conditions

Noonan syndrome 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.001	GERP -3.8, phastCons 0.046
Overall
CADD	8.226	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00344% South Asian · 3/87,230 alleles

Filtering AF 0.000914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000453%

Overall 0.000627% 10/1,594,020 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00344%	29,077
Remaining individualsnot grpmax-eligible	0.00162%	61,618
African / African-American	0.00135%	73,818
European (non-Finnish)	0.000426%	234,585

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.Pro799=
Coding: c.2397G>A
MANE Select: NM_006939
dbSNP: rs770022419
Type: single nucleotide variant
Location: chr14:50145584 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 74.67 · 11 PDB
Residue 799: the ras-gef domain; an α-helix

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.Pro799Leu Uncertain significance ★★ ⚠ same residue
SOS2 p.Pro799Ser 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-pro799 (accessed [today's date]).

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