Is SHANK3 p.Pro985fs (c.2951dup) pathogenic?

SHANK3 p.Pro985fs (c.2951dup) is classified Likely pathogenic in SHANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-17). No allele count reported in gnomAD v4.1 (AN 1,091,354).

How common is SHANK3 p.Pro985fs (c.2951dup) in the general population?

SHANK3 p.Pro985fs (c.2951dup) is no allele count reported in gnomAD v4.1 (AN 1,091,354) (gnomAD).

SHANK3 p.Pro985fs

c.2951dup · rs1603447111 · VCV817242

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,091,354)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 22 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.85, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,091,354). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SHANK3
Protein: p.Pro985fs
Coding: c.2951dup
MANE Select: NM_001372044
dbSNP: rs1603447111
Type: Duplication
Location: chr22:50720554 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.36 · 3 PDB
Residue 985: the 'disordered' region

Full SHANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SHANK3 p.Ala1289fs Pathogenic ★★ same type
SHANK3 p.Ala1302fs Pathogenic ★★ same type
SHANK3 p.Leu1615fs Pathogenic ★★ same type
SHANK3 c.1530-280dup Benign/Likely benign ★★ same type
SHANK3 c.244dup Likely pathogenic ★ same type
SHANK3 c.3763dupC Pathogenic ★ same type
SHANK3 c.4818dupC Pathogenic ★ same type
SHANK3 p.Ala1331fs Pathogenic ★ 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/shank3-p-pro985fs (accessed [today's date]).

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