Is SHANK2 p.Pro106= (c.318G>A) pathogenic?

SHANK2 p.Pro106= (c.318G>A) is classified Likely benign in SHANK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-17). Ultra-rare (popmax 0.0562%, eas); Associated with SHANK2-related disorder.

What condition is associated with SHANK2 p.Pro106= (c.318G>A)?

SHANK2 p.Pro106= (c.318G>A) is associated with SHANK2-related disorder (ClinVar).

How common is SHANK2 p.Pro106= (c.318G>A) in the general population?

SHANK2 p.Pro106= (c.318G>A) is ultra-rare (popmax 0.0562%, eas) (gnomAD).

SHANK2 p.Pro106=

c.318G>A · rs141716902 · VCV3047435

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0562%, eas)

Conditions

SHANK2-related disorder

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 -4.6
Overall
CADD	7.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0562% East Asian · 23/40,924 alleles

Filtering AF 0.0383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.0069% 107/1,551,748 alleles · ultra-rare exomes 93/1,399,418 · genomes 14/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0562%	1,779
African / African-American	0.0342%	2,927
Middle Eastern	0.0334%	2,996
Remaining individualsnot grpmax-eligible	0.0333%	3,006
South Asian	0.00714%	14,011
European (non-Finnish)	0.0027%	37,000

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: SHANK2
Protein: p.Pro106=
Coding: c.318G>A
MANE Select: NM_012309
dbSNP: rs141716902
Type: single nucleotide variant
Location: chr11:71118922 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.58 · 2 PDB

Full SHANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SHANK2-related disorder

Similar variants

SHANK2 p.Gln127Ter Likely pathogenic ★ same condition
SHANK2 p.Gln799Ter Likely pathogenic ★ same condition
SHANK2 p.Arg1636Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
SHANK2 p.Arg766Trp Uncertain significance ★ same condition
SHANK2 p.Arg864Trp Uncertain significance ★ same condition
SHANK2 p.Gly570Ser Uncertain significance ★ same condition
SHANK2 p.Ser1742Ile Uncertain significance ★ ⚠ same condition
SHANK2 p.Thr1176Met 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/shank2-p-pro106 (accessed [today's date]).

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