Is ADNP2 p.Met652Val (c.1954A>G) pathogenic?

ADNP2 p.Met652Val (c.1954A>G) is classified Likely benign in ADNP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0582); Very rare (popmax 0.00446%, eas).

How common is ADNP2 p.Met652Val (c.1954A>G) in the general population?

ADNP2 p.Met652Val (c.1954A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ADNP2 p.Met652Val (c.1954A>G)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

ADNP2 p.Met652Val

c.1954A>G · VCV4019359

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -4.66	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 0.22	GERP -2.8, phastCons 0.055
Regional constraint	o/e 0.94	unconstrained · MANE · 1,556 bp · p 0.14 · regional, not allelic
Overall
CADD	0.031	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 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00167% 27/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,442
African / African-American	0.00267%	37,460
European (non-Finnish)	0.00186%	53,638
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: ADNP2
Protein: p.Met652Val
Coding: c.1954A>G
MANE Select: NM_014913
Type: single nucleotide variant
Location: chr18:80137367 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 58.42

Full ADNP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADNP2 p.Gly54Val Uncertain significance ★★ ⚠ same type
ADNP2 p.Ala222Thr Uncertain significance ★ ⚠ same type
ADNP2 p.Ala271Val Uncertain significance ★ ⚠ same type
ADNP2 p.Ala287Thr Uncertain significance ★ ⚠ same type
ADNP2 p.Ala326Pro Uncertain significance ★ ⚠ same type
ADNP2 p.Ala451Gly Uncertain significance ★ ⚠ same type
ADNP2 p.Ala493Ser Uncertain significance ★ ⚠ same type
ADNP2 p.Ala511Thr Uncertain significance ★ ⚠ 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/adnp2-p-met652val (accessed [today's date]).

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