Is SHANK2 p.Pro792Ser (c.2374C>T) pathogenic?

SHANK2 p.Pro792Ser (c.2374C>T) is classified Pathogenic in SHANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.0538); Absent from gnomAD v4.1; Associated with autism, susceptibility to, 17.

What condition is associated with SHANK2 p.Pro792Ser (c.2374C>T)?

SHANK2 p.Pro792Ser (c.2374C>T) is associated with autism, susceptibility to, 17 (ClinVar).

How common is SHANK2 p.Pro792Ser (c.2374C>T) in the general population?

SHANK2 p.Pro792Ser (c.2374C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SHANK2 p.Pro792Ser (c.2374C>T)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

SHANK2 p.Pro792Ser

c.2374C>T · VCV3897810

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

autism, susceptibility to, 17

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign ⚠ discordant with ClinVar
REVEL	0.086	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP -2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 173 kb · p 1.1e-09 · regional, not allelic
Overall
CADD	4.225	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P413S vs ClinVar P792S) — verify the residue.

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.Pro792Ser
Coding: c.2374C>T
MANE Select: NM_012309
Type: single nucleotide variant
Location: chr11:70492400 (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

autism, susceptibility to, 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SHANK2 p.Pro792= Benign/Likely benign ★★ same residue
SHANK2 c.2439+1G>A Pathogenic/Likely pathogenic ★★ same condition
SHANK2 p.Arg185Ter Pathogenic ★★ same condition
SHANK2 p.Arg841Ter Pathogenic ★★ same condition
SHANK2 p.Glu252Ter Likely pathogenic ★★ same condition
SHANK2 p.Arg1089His Uncertain significance ★★ same condition
SHANK2 p.Ile1664Thr Benign/Likely benign ★★ same condition
SHANK2 p.Thr1675= Benign/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/shank2-p-pro792ser (accessed [today's date]).

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