Is SHANK2 p.Asp295= (c.885T>C) pathogenic?

SHANK2 p.Asp295= (c.885T>C) is classified Likely benign in SHANK2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-15). Absent from gnomAD v4.1; Associated with SHANK2-related disorder.

What condition is associated with SHANK2 p.Asp295= (c.885T>C)?

SHANK2 p.Asp295= (c.885T>C) is associated with SHANK2-related disorder (ClinVar).

How common is SHANK2 p.Asp295= (c.885T>C) in the general population?

SHANK2 p.Asp295= (c.885T>C) is absent from gnomAD v4.1 (gnomAD).

SHANK2 p.Asp295=

c.885T>C · rs1951535084 · VCV3031430

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

SHANK2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.489	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -4.5
Overall
CADD	0.386	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: SHANK2
Protein: p.Asp295=
Coding: c.885T>C
MANE Select: NM_012309
dbSNP: rs1951535084
Type: single nucleotide variant
Location: chr11:71092449 (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-asp295 (accessed [today's date]).

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