Is ADAP2 p.Gly21Ser (c.61G>A) pathogenic?

ADAP2 p.Gly21Ser (c.61G>A) is classified Uncertain significance in ADAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.456); Very rare (popmax 0.00294%, sas).

How common is ADAP2 p.Gly21Ser (c.61G>A) in the general population?

ADAP2 p.Gly21Ser (c.61G>A) is very rare (popmax 0.00294%, sas) (gnomAD).

What do computational predictors say about ADAP2 p.Gly21Ser (c.61G>A)?

AlphaMissense predicts ambiguous (score 0.456) — an in-silico prediction, not a clinical call.

ADAP2 p.Gly21Ser

c.61G>A · VCV4233716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00294%, sas)

Computational evidence

Protein change
AlphaMissense	0.456	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -8.16	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 0.019 · regional, not allelic
Overall
CADD	28.6	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 0.00294% South Asian · 1/34,010 alleles

Overall 8.98e-05% 1/1,113,772 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: ADAP2
Protein: p.Gly21Ser
Coding: c.61G>A
MANE Select: NM_018404
Type: single nucleotide variant
Location: chr17:30922075 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.49
Residue 21: the arf-gap domain

Full ADAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP2 p.Ala279Thr Uncertain significance ★ ⚠ same type
ADAP2 p.Ala36Ser Uncertain significance ★ ⚠ same type
ADAP2 p.Arg16Gly Uncertain significance ★ ⚠ same type
ADAP2 p.Arg209Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg229His Uncertain significance ★ ⚠ same type
ADAP2 p.Arg254Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg285Gln Uncertain significance ★ ⚠ same type
ADAP2 p.Arg322Gln 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/adap2-p-gly21ser (accessed [today's date]).

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