Is ADNP p.Pro273Ser (c.817C>T) pathogenic?

ADNP p.Pro273Ser (c.817C>T) is classified Uncertain significance in ADNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-13). AlphaMissense: likely pathogenic (0.708); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Pro273Ser (c.817C>T)?

ADNP p.Pro273Ser (c.817C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Pro273Ser (c.817C>T) in the general population?

ADNP p.Pro273Ser (c.817C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADNP p.Pro273Ser (c.817C>T)?

AlphaMissense predicts likely pathogenic (score 0.708) — an in-silico prediction, not a clinical call.

ADNP p.Pro273Ser

c.817C>T · VCV3838537

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.708 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.708	likely pathogenic
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 536 bp · p 0.077 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro273Ser
Coding: c.817C>T
MANE Select: NM_001282531
Type: single nucleotide variant
Location: chr20:50893897 (GRCh38)
Gene constraint: LOEUF 0.106 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.07

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADNP p.Pro273= Likely benign ★ same residue
ADNP p.Ser738Ter Pathogenic ★★ same condition
ADNP p.Trp446Ter Pathogenic ★★ same condition
ADNP p.Arg264Gln Uncertain significance ★★ ⚠ same condition
ADNP p.Arg296Gln Uncertain significance ★★ ⚠ same condition
ADNP p.Asn331Tyr Uncertain significance ★★ ⚠ same condition
ADNP p.Asn951Ser Uncertain significance ★★ ⚠ same condition
ADNP p.Gln302His 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-pro273ser (accessed [today's date]).

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