Is SHANK3 p.Arg290= (c.870C>T) pathogenic?

SHANK3 p.Arg290= (c.870C>T) is classified Likely benign in SHANK3 (ClinVar, Single submitter, 2 submitters; last evaluated 2017-09-08). Ultra-rare (popmax 0.0125%, amr); Associated with Inborn genetic diseases.

What condition is associated with SHANK3 p.Arg290= (c.870C>T)?

SHANK3 p.Arg290= (c.870C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SHANK3 p.Arg290= (c.870C>T) in the general population?

SHANK3 p.Arg290= (c.870C>T) is ultra-rare (popmax 0.0125%, amr) (gnomAD).

SHANK3 p.Arg290=

c.870C>T · rs760387314 · VCV1753643

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0125%, amr)

Conditions

Inborn genetic diseases

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 -11	GERP -4.4
Overall
CADD	1.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0125% Admixed American · 7/55,804 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00414%

Overall 0.00208% 33/1,588,250 alleles · ultra-rare exomes 29/1,436,110 · genomes 4/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0125%	7,972
East Asian	0.00918%	10,887
European (non-Finnish)	0.00171%	58,414
African / African-American	0.00134%	74,420
South Asian	0.00114%	87,686

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: SHANK3
Protein: p.Arg290=
Coding: c.870C>T
MANE Select: NM_001372044
dbSNP: rs760387314
Type: single nucleotide variant
Location: chr22:50679063 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.36 · 3 PDB

Full SHANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SHANK3 p.Arg290His Uncertain significance ★ same residue
SHANK3 p.Arg290Leu Uncertain significance ★ same residue
SHANK3 p.Arg166Ter Pathogenic/Likely pathogenic ★★ same condition
SHANK3 p.Gln1543Ter Pathogenic/Likely pathogenic ★★ same condition
SHANK3 c.2279G>A Uncertain significance ★★ same condition
SHANK3 p.Ala901Thr Uncertain significance ★★ same condition
SHANK3 p.Arg1298Ser Uncertain significance ★★ same condition
SHANK3 p.Arg1537Cys 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/shank3-p-arg290 (accessed [today's date]).

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