Is SHANK2 p.Ser764= (c.2292G>A) pathogenic?

SHANK2 p.Ser764= (c.2292G>A) is classified Likely benign in SHANK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-01). Very rare (popmax 0.00225%, eas).

How common is SHANK2 p.Ser764= (c.2292G>A) in the general population?

SHANK2 p.Ser764= (c.2292G>A) is very rare (popmax 0.00225%, eas) (gnomAD).

SHANK2 p.Ser764=

c.2292G>A · rs782696929 · VCV436711

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.091	GERP -3.5, phastCons 0.93
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% East Asian · 1/44,428 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.00256% 41/1,602,700 alleles · very rare exomes 34/1,450,634 · genomes 7/152,066 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0509%	1,964
East Asiangrpmax	0.00225%	44,428
Remaining individualsnot grpmax-eligible	0.00161%	62,006
African / African-American	0.00134%	74,734
European (non-Finnish)	0.000511%	195,805

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser764=
Coding: c.2292G>A
MANE Select: NM_012309
dbSNP: rs782696929
Type: single nucleotide variant
Location: chr11:70500586 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.58 · 2 PDB
Residue 764: the 'disordered' region

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

Similar variants

SHANK2 c.2439+1G>A Pathogenic/Likely pathogenic ★★ same type
SHANK2 p.Arg185Ter Pathogenic ★★ same type
SHANK2 p.Arg642Ter Pathogenic ★★ same type
SHANK2 p.Arg841Ter Pathogenic ★★ same type
SHANK2 p.Gln663Ter Likely pathogenic ★★ same type
SHANK2 p.Glu252Ter Likely pathogenic ★★ same type
SHANK2 p.Ala1729Thr Uncertain significance ★★ ⚠ same type
SHANK2 p.Arg1089His Uncertain significance ★★ same type

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-ser764 (accessed [today's date]).

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