Is ADNP p.Ser396fs (c.1184dup) pathogenic?

ADNP p.Ser396fs (c.1184dup) is classified Pathogenic in ADNP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-12-01). Absent from gnomAD; Associated with intellectual disability.

What condition is associated with ADNP p.Ser396fs (c.1184dup)?

ADNP p.Ser396fs (c.1184dup) is associated with intellectual disability (ClinVar).

How common is ADNP p.Ser396fs (c.1184dup) in the general population?

ADNP p.Ser396fs (c.1184dup) is absent from gnomAD (gnomAD).

ADNP p.Ser396fs

c.1184dup · rs1981038382 · VCV973125

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability

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	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: ADNP
Protein: p.Ser396fs
Coding: c.1184dup
MANE Select: NM_001282531
dbSNP: rs1981038382
Type: Duplication
Location: chr20:50893529 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 396: the 'disordered' region

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Arg216Ter Pathogenic ★★ same condition
ADNP p.Leu831fs Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Ile1069Val Uncertain significance ★★ ⚠ same condition
ADNP c.-89-3923_201+2793inv Likely pathogenic ★ same condition
ADNP p.Gln414fs Pathogenic ★ same condition
ADNP p.Gln414Ter Pathogenic ★ same condition
ADNP p.Leu23fs Pathogenic ★ same condition
ADNP p.Arg296Trp 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/adnp-p-ser396fs (accessed [today's date]).

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