Is SHOC2 p.Arg190= (c.570G>A) pathogenic?

SHOC2 p.Arg190= (c.570G>A) is classified Likely benign in SHOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). Very rare (popmax 0.00267%, afr); Associated with RASopathy.

What condition is associated with SHOC2 p.Arg190= (c.570G>A)?

SHOC2 p.Arg190= (c.570G>A) is associated with RASopathy (ClinVar).

How common is SHOC2 p.Arg190= (c.570G>A) in the general population?

SHOC2 p.Arg190= (c.570G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

SHOC2 p.Arg190=

c.570G>A · VCV4751772

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.85	GERP -1.2, phastCons 0.99
Overall
CADD	9.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,868 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,558 alleles · very rare exomes 1/1,461,476 · genomes 1/152,082 · 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: SHOC2
Protein: p.Arg190=
Coding: c.570G>A
MANE Select: NM_007373
Type: single nucleotide variant
Location: chr10:110964928 (GRCh38)
Gene constraint: LOEUF 0.201 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 13 PDB
Residue 190: an α-helix

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.Arg190Gly Uncertain significance ★ ⚠ same residue
SHOC2 p.Arg190Lys Uncertain significance ★ ⚠ same residue
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

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-arg190 (accessed [today's date]).

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