Is AAGAB p.Arg161Gln (c.482G>A) pathogenic?

AAGAB p.Arg161Gln (c.482G>A) is classified Uncertain significance in AAGAB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.8927); Very rare (popmax 0.00221%, nfe).

How common is AAGAB p.Arg161Gln (c.482G>A) in the general population?

AAGAB p.Arg161Gln (c.482G>A) is very rare (popmax 0.00221%, nfe) (gnomAD).

What do computational predictors say about AAGAB p.Arg161Gln (c.482G>A)?

AlphaMissense predicts likely pathogenic (score 0.8927) — an in-silico prediction, not a clinical call.

AAGAB p.Arg161Gln

c.482G>A · rs779782680 · VCV2211104

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8927 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8927	likely pathogenic
REVEL	0.651	pathogenic-leaning
SaProt	LLR -14.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 52 kb · p 8.1e-05 · regional, not allelic
Overall
CADD	30.0	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 0.00221% European (non-Finnish) · 26/1,178,324 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00186% 30/1,611,820 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
European (non-Finnish)grpmax	0.00221%	45,320
South Asian	0.0022%	45,528
Remaining individualsnot grpmax-eligible	0.0016%	62,376

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: AAGAB
Protein: p.Arg161Gln
Coding: c.482G>A
MANE Select: NM_024666
dbSNP: rs779782680
Type: single nucleotide variant
Location: chr15:67231867 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 3 PDB
Residue 161: an α-helix

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

Similar variants

AAGAB p.Arg161Ter Pathogenic ★★ same residue
AAGAB p.Arg124Ter Pathogenic ★★ same type
AAGAB p.Gln21Ter Pathogenic ★★ same type
AAGAB p.Ala74Pro Uncertain significance ★★ ⚠ same type
AAGAB p.Leu92Val Uncertain significance ★★ ⚠ same type
AAGAB c.264+33A>G Benign ★★ same type
AAGAB c.536-95G>A Benign ★★ same type
AAGAB c.618+18A>G Benign ★★ 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/aagab-p-arg161gln (accessed [today's date]).

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