Is SOS1 p.Ser484= (c.1452C>T) pathogenic?

SOS1 p.Ser484= (c.1452C>T) is classified Likely benign in SOS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-10). Very rare (popmax 0.000424%, nfe); Associated with RASopathy.

What condition is associated with SOS1 p.Ser484= (c.1452C>T)?

SOS1 p.Ser484= (c.1452C>T) is associated with RASopathy (ClinVar).

How common is SOS1 p.Ser484= (c.1452C>T) in the general population?

SOS1 p.Ser484= (c.1452C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

SOS1 p.Ser484=

c.1452C>T · VCV4779181

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 4.4, phastCons 1
Overall
CADD	12.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,790 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000547% 8/1,461,604 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,247
Finnishnot grpmax-eligible	0.00156%	63,930
European (non-Finnish)grpmax	0.000424%	235,958

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SOS1
Protein: p.Ser484=
Coding: c.1452C>T
MANE Select: NM_005633
Type: single nucleotide variant
Location: chr2:39022976 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.12 · 92 PDB
Residue 484: the ph domain

Full SOS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

HGF p.Val484Ile Uncertain significance ★ ⚠ same residue
SOS1 p.Ser484Arg Uncertain significance ⚠ same residue
SOS1 p.Arg552Gly Pathogenic ★★★ ⚠ same condition
SOS1 p.Arg552Lys Pathogenic ★★★ ⚠ same condition
SOS1 p.Arg552Met Likely pathogenic ★★★ ⚠ same condition
SOS1 p.Arg552Ser Pathogenic ★★★ ⚠ same condition
SOS1 p.Arg552Thr Pathogenic ★★★ ⚠ same condition
SOS1 p.Arg552Trp 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/sos1-p-ser484 (accessed [today's date]).

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