Is ADNP p.Ser404Ter (c.1211C>A) pathogenic?

ADNP p.Ser404Ter (c.1211C>A) is classified Pathogenic in ADNP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-04-01). Absent from gnomAD v4.1; Associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.

How common is ADNP p.Ser404Ter (c.1211C>A) in the general population?

ADNP p.Ser404Ter (c.1211C>A) is absent from gnomAD v4.1 (gnomAD).

ADNP p.Ser404Ter

Q: What condition is associated with ADNP p.Ser404Ter (c.1211C>A)?

ADNP p.Ser404Ter (c.1211C>A) is associated with ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

c.1211C>A · rs587777524 · VCV139633

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADNP
Protein: p.Ser404Ter
Coding: c.1211C>A
MANE Select: NM_001282531
dbSNP: rs587777524
Type: single nucleotide variant
Location: chr20:50893503 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07
Residue 404: the 'disordered' region

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.Ser404= Benign ★ same residue
ADNP p.Arg173Ter Pathogenic ★★ same condition
ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same condition
ADNP p.Ser738Ter Pathogenic ★★ same condition
ADNP p.Trp446Ter Pathogenic ★★ same condition
ADNP p.Tyr172Ter Likely pathogenic ★★ same condition
ADNP p.Tyr378Ter 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-ser404ter (accessed [today's date]).

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