Is SHOC2 p.Lys9= (c.27A>G) pathogenic?

SHOC2 p.Lys9= (c.27A>G) is classified Likely benign in SHOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-30). Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with SHOC2 p.Lys9= (c.27A>G)?

SHOC2 p.Lys9= (c.27A>G) is associated with RASopathy (ClinVar).

How common is SHOC2 p.Lys9= (c.27A>G) in the general population?

SHOC2 p.Lys9= (c.27A>G) is absent from gnomAD v4.1 (gnomAD).

SHOC2 p.Lys9=

c.27A>G · rs150364514 · VCV1963211

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 6.2	GERP 1.4, phastCons 1
Overall
CADD	10.48	PHRED · no single calibrated threshold — expert panels disagree

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: SHOC2
Protein: p.Lys9=
Coding: c.27A>G
MANE Select: NM_007373
dbSNP: rs150364514
Type: single nucleotide variant
Location: chr10:110964385 (GRCh38)
Gene constraint: LOEUF 0.201 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 13 PDB
Residue 9: the 'disordered' region

Full SHOC2 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

SHOC2 p.Met173Ile Pathogenic ★★★ ⚠ same condition
SHOC2 p.Ser2Gly Pathogenic ★★★ ⚠ same condition
SHOC2 c.-1C>T Uncertain significance ★★★ same condition
SHOC2 p.Tyr189Phe Uncertain significance ★★★ ⚠ same condition
SHOC2 c.1423-7C>T Benign ★★★ same condition
SHOC2 c.1540+8C>A Likely benign ★★★ same condition
SHOC2 c.1540+8C>T Likely benign ★★★ same condition
SHOC2 p.Ala298= 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/shoc2-p-lys9 (accessed [today's date]).

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