Is ADAP1 p.Lys302Asn (c.906G>C) pathogenic?

ADAP1 p.Lys302Asn (c.906G>C) is classified Uncertain significance in ADAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: ambiguous (0.5411); Very rare (popmax 0.000508%, nfe).

How common is ADAP1 p.Lys302Asn (c.906G>C) in the general population?

ADAP1 p.Lys302Asn (c.906G>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about ADAP1 p.Lys302Asn (c.906G>C)?

AlphaMissense predicts ambiguous (score 0.5411) — an in-silico prediction, not a clinical call.

ADAP1 p.Lys302Asn

c.906G>C · VCV4637858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5411	ambiguous
REVEL	0.14	moderately benign-leaning
SaProt	LLR -10.85	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP 0.27, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 56 kb · p 0.32 · regional, not allelic
Overall
CADD	21.5	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 0.000508% European (non-Finnish) · 6/1,179,978 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,686 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: ADAP1
Protein: p.Lys302Asn
Coding: c.906G>C
MANE Select: NM_006869
Type: single nucleotide variant
Location: chr7:899223 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.96 · 4 PDB
Residue 302: the ph 2 domain; an α-helix

Full ADAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP1 p.Ala168Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala182Thr Uncertain significance ★ same type
ADAP1 p.Ala243Thr Uncertain significance ★ ⚠ same type
ADAP1 p.Ala26Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala293Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala349Val Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Glu Uncertain significance ★ ⚠ same type
ADAP1 p.Ala81Val 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/adap1-p-lys302asn (accessed [today's date]).

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