Is ADAP1 p.Arg149Gln (c.446G>A) pathogenic?

ADAP1 p.Arg149Gln (c.446G>A) is classified Uncertain significance in ADAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely pathogenic (0.9934); Very rare (popmax 0.00891%, eas).

How common is ADAP1 p.Arg149Gln (c.446G>A) in the general population?

ADAP1 p.Arg149Gln (c.446G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ADAP1 p.Arg149Gln (c.446G>A)?

AlphaMissense predicts likely pathogenic (score 0.9934) — an in-silico prediction, not a clinical call.

ADAP1 p.Arg149Gln

c.446G>A · rs561202230 · VCV2593488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9934	likely pathogenic · top 9% in ADAP1
REVEL	0.436	indeterminate
SaProt	LLR -13.93	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 4.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 56 kb · p 0.32 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00378% 61/1,612,450 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Remaining individualsnot grpmax-eligible	0.0112%	8,925
East Asiangrpmax	0.00891%	11,222
European (non-Finnish)	0.0022%	45,380
Admixed American	0.00167%	60,024
Finnishnot grpmax-eligible	0.0016%	62,452
South Asian	0.0011%	91,090

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg149Gln
Coding: c.446G>A
MANE Select: NM_006869
dbSNP: rs561202230
Type: single nucleotide variant
Location: chr7:905115 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.96 · 4 PDB
Residue 149: the ph 1 domain; a β-strand

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-arg149gln (accessed [today's date]).

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