Is SOS2 p.Pro102Ser (c.304C>T) pathogenic?

SOS2 p.Pro102Ser (c.304C>T) is classified Uncertain significance in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-24). AlphaMissense: ambiguous (0.3868); Very rare (popmax 8.48e-05%, nfe); Associated with Noonan syndrome 9.

What condition is associated with SOS2 p.Pro102Ser (c.304C>T)?

SOS2 p.Pro102Ser (c.304C>T) is associated with Noonan syndrome 9 (ClinVar).

How common is SOS2 p.Pro102Ser (c.304C>T) in the general population?

SOS2 p.Pro102Ser (c.304C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about SOS2 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts ambiguous (score 0.3868) — an in-silico prediction, not a clinical call.

SOS2 p.Pro102Ser

c.304C>T · rs2139783538 · VCV1485702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Noonan syndrome 9

Computational evidence

Protein change
AlphaMissense	0.3868	ambiguous
REVEL	0.514	indeterminate
SaProt	LLR -3.08	tolerated
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	25.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.2e-05% 1/1,613,916 alleles · very rare exomes 1/1,461,732 · genomes 0/152,184 · joint denominator

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.Pro102Ser
Coding: c.304C>T
MANE Select: NM_006939
dbSNP: rs2139783538
Type: single nucleotide variant
Location: chr14:50200994 (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.Pro102Leu 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-pro102ser (accessed [today's date]).

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