Is ADNP p.Ser738fs (c.2212dup) pathogenic?

ADNP p.Ser738fs (c.2212dup) is classified Pathogenic in ADNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-08). Absent from gnomAD; Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Ser738fs (c.2212dup) in the general population?

ADNP p.Ser738fs (c.2212dup) is absent from gnomAD (gnomAD).

ADNP p.Ser738fs

Q: What condition is associated with ADNP p.Ser738fs (c.2212dup)?

ADNP p.Ser738fs (c.2212dup) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.2212dup · rs2515579850 · VCV1804918

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

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 10	GERP 1.9, 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.Ser738fs
Coding: c.2212dup
MANE Select: NM_001282531
dbSNP: rs2515579850
Type: Duplication
Location: chr20:50892501 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 738: a modified residue (phosphoserine)

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

Disease context

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Ser738Ter Pathogenic ★★ same residue
ADNP p.Asn905Ter Likely pathogenic ★★ same condition
ADNP p.Ile22fs Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Thr64fs Pathogenic ★★ same condition
ADNP p.Val1084fs Uncertain significance ★★ same condition
ADNP p.Ser141dup Benign/Likely benign ★★ same condition
ADNP p.Asn398Ter Pathogenic ★ same condition
ADNP p.Asp60fs Pathogenic ★ 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-ser738fs (accessed [today's date]).

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