Is ADNP p.Ser134= (c.402C>T) pathogenic?

ADNP p.Ser134= (c.402C>T) is classified Likely benign in ADNP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Ser134= (c.402C>T)?

ADNP p.Ser134= (c.402C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADNP p.Ser134= (c.402C>T) in the general population?

ADNP p.Ser134= (c.402C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

ADNP p.Ser134=

c.402C>T · rs778855131 · VCV735278

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.6, phastCons 1
Overall
CADD	14.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,900 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00105% 17/1,613,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,983
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000848%	117,991

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ADNP
Protein: p.Ser134=
Coding: c.402C>T
MANE Select: NM_001282531
dbSNP: rs778855131
Type: single nucleotide variant
Location: chr20:50894312 (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.Ser134Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Ser134Arg Uncertain significance ★ ⚠ 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

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-ser134 (accessed [today's date]).

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