Is SHOC2 p.Arg98= (c.294G>A) pathogenic?

SHOC2 p.Arg98= (c.294G>A) is classified Likely benign in SHOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with SHOC2 p.Arg98= (c.294G>A)?

SHOC2 p.Arg98= (c.294G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is SHOC2 p.Arg98= (c.294G>A) in the general population?

SHOC2 p.Arg98= (c.294G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

SHOC2 p.Arg98=

c.294G>A · VCV3441519

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -3.1, phastCons 1
Overall
CADD	7.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000124% 2/1,614,066 alleles · ultra-rare exomes 2/1,461,828 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,179,984

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.Arg98=
Coding: c.294G>A
MANE Select: NM_007373
Type: single nucleotide variant
Location: chr10:110964652 (GRCh38)
Gene constraint: LOEUF 0.201 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 13 PDB
Residue 98: an α-helix

Full SHOC2 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

SHOC2 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
SHOC2 p.Ala304Thr Uncertain significance ★★ ⚠ same condition
SHOC2 p.Ala580Thr Uncertain significance ★★ ⚠ same condition
SHOC2 p.Arg366Gln Uncertain significance ★★ ⚠ same condition
SHOC2 p.Asn248Thr Uncertain significance ★★ ⚠ same condition
SHOC2 p.Asp210Asn Uncertain significance ★★ ⚠ same condition
SHOC2 p.Asp49Asn Uncertain significance ★★ ⚠ same condition
SHOC2 p.Gln229Lys 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/shoc2-p-arg98 (accessed [today's date]).

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