Is SOS1 p.Pro1237Leu (c.3710C>T) pathogenic?

SOS1 p.Pro1237Leu (c.3710C>T) is classified Uncertain significance in SOS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.0971); Absent from gnomAD v4.1.

How common is SOS1 p.Pro1237Leu (c.3710C>T) in the general population?

SOS1 p.Pro1237Leu (c.3710C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SOS1 p.Pro1237Leu (c.3710C>T)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

SOS1 p.Pro1237Leu

c.3710C>T · VCV3901589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.521	indeterminate
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,424 bp · p 0.35 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SOS1
Protein: p.Pro1237Leu
Coding: c.3710C>T
MANE Select: NM_005633
Type: single nucleotide variant
Location: chr2:38986116 (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 1237: the 'disordered' region

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

Similar variants

SOS1 p.Pro1237Thr Likely benign ★★★ same residue
SOS1 p.Pro1237Ser Uncertain significance ★★ ⚠ same residue
SOS1 p.Pro1237Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
SOS1 p.Arg552Gly Pathogenic ★★★ ⚠ same type
SOS1 p.Arg552Lys Pathogenic ★★★ ⚠ same type
SOS1 p.Arg552Met Likely pathogenic ★★★ ⚠ same type
SOS1 p.Arg552Ser Pathogenic ★★★ ⚠ same type
SOS1 p.Arg552Thr Pathogenic ★★★ ⚠ same type

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-pro1237leu (accessed [today's date]).

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