Is ADNP p.Ala157Ser (c.469G>T) pathogenic?

ADNP p.Ala157Ser (c.469G>T) is classified Likely benign in ADNP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.0924); Very rare (popmax 0.00102%, nfe).

How common is ADNP p.Ala157Ser (c.469G>T) in the general population?

ADNP p.Ala157Ser (c.469G>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about ADNP p.Ala157Ser (c.469G>T)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

ADNP p.Ala157Ser

c.469G>T · rs557449743 · VCV2183897

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 437 bp · p 7.5e-05 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,038 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,012 alleles · very rare

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.Ala157Ser
Coding: c.469G>T
MANE Select: NM_001282531
dbSNP: rs557449743
Type: single nucleotide variant
Location: chr20:50894245 (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

Similar variants

ADNP p.Arg173Ter Pathogenic ★★ same type
ADNP p.Arg216Ter Pathogenic ★★ same type
ADNP p.Arg225Ter Pathogenic/Likely pathogenic ★★ same type
ADNP p.Arg306Ter Pathogenic/Likely pathogenic ★★ same type
ADNP p.Arg730Ter Pathogenic/Likely pathogenic ★★ same type
ADNP p.Ser738Ter Pathogenic ★★ same type
ADNP p.Trp446Ter Pathogenic ★★ same type
ADNP p.Tyr172Ter Likely pathogenic ★★ same type

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-ala157ser (accessed [today's date]).

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