Is SHANK2 p.Pro1747= (c.5241C>T) pathogenic?

SHANK2 p.Pro1747= (c.5241C>T) is classified Likely benign in SHANK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). Very rare (popmax 0.000509%, nfe); Associated with SHANK2-related disorder.

What condition is associated with SHANK2 p.Pro1747= (c.5241C>T)?

SHANK2 p.Pro1747= (c.5241C>T) is associated with SHANK2-related disorder (ClinVar).

How common is SHANK2 p.Pro1747= (c.5241C>T) in the general population?

SHANK2 p.Pro1747= (c.5241C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

SHANK2 p.Pro1747=

c.5241C>T · rs782236024 · VCV3044938

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

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 3.4	GERP -2.5, phastCons 1
Overall
CADD	9.523	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,456 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,440 alleles · very rare exomes 5/1,461,188 · genomes 1/152,252 · joint denominator

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.Pro1747=
Coding: c.5241C>T
MANE Select: NM_012309
dbSNP: rs782236024
Type: single nucleotide variant
Location: chr11:70473178 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.58 · 2 PDB
Residue 1747: the 'disordered' region

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-pro1747 (accessed [today's date]).

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