Is ADNP p.Pro131= (c.393G>A) pathogenic?

ADNP p.Pro131= (c.393G>A) is classified Benign/Likely benign in ADNP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-08-14). Rare (popmax 0.813%, eas); Associated with Inborn genetic diseases.

What condition is associated with ADNP p.Pro131= (c.393G>A)?

ADNP p.Pro131= (c.393G>A) is associated with Inborn genetic diseases, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (ClinVar).

How common is ADNP p.Pro131= (c.393G>A) in the general population?

ADNP p.Pro131= (c.393G>A) is rare (popmax 0.813%, eas) (gnomAD).

ADNP p.Pro131=

c.393G>A · rs201360495 · VCV588351

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.813%, eas)

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 0.2	GERP -0.79, phastCons 0.99
Overall
CADD	10.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.813% East Asian · 365/44,892 alleles

Filtering AF 0.744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.0233% 376/1,613,598 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.813%	123
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.008%	12,496
South Asian	0.0011%	90,958
European (non-Finnish)	0.000339%	294,978

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.Pro131=
Coding: c.393G>A
MANE Select: NM_001282531
dbSNP: rs201360495
Type: single nucleotide variant
Location: chr20:50894321 (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

Also linked: ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

Similar variants

ADNP p.Pro131Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ADNP p.Pro131Ser Uncertain significance ★ ⚠ same residue
ADNP p.Pro131Ala Uncertain significance ⚠ 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

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-pro131 (accessed [today's date]).

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