Is SOS2 p.Ser412= (c.1236C>T) pathogenic?

SOS2 p.Ser412= (c.1236C>T) is classified Likely benign in SOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). Very rare (popmax 0.00134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with SOS2 p.Ser412= (c.1236C>T)?

SOS2 p.Ser412= (c.1236C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is SOS2 p.Ser412= (c.1236C>T) in the general population?

SOS2 p.Ser412= (c.1236C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

SOS2 p.Ser412=

c.1236C>T · rs768171476 · VCV1756902

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Cardiovascular phenotype

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 4.4	GERP 0.076, phastCons 1
Overall
CADD	9.548	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,820 alleles

Overall 0.000124% 2/1,613,478 alleles · very rare exomes 1/1,461,410 · genomes 1/152,068 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,820
European (non-Finnish)	8.48e-05%	1,179,837

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.Ser412=
Coding: c.1236C>T
MANE Select: NM_006939
dbSNP: rs768171476
Type: single nucleotide variant
Location: chr14:50160047 (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

Similar variants

SOS2 p.Ser412Arg Uncertain significance ★ ⚠ same residue
SOS2 p.Ser412Ile Uncertain significance ★ same residue
SOS2 c.346-3C>T Uncertain significance ★★ same condition
SOS2 p.Ala1119Val Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala62Val Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala743Gly Uncertain significance ★★ ⚠ same condition
SOS2 p.Ala890Thr Uncertain significance ★★ ⚠ same condition
SOS2 p.Arg1222Leu 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-ser412 (accessed [today's date]).

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