Is ATL2 p.Arg322Gln (c.965G>A) pathogenic?

ATL2 p.Arg322Gln (c.965G>A) is classified Likely benign in ATL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.0658); Rare (popmax 0.49%, nfe).

How common is ATL2 p.Arg322Gln (c.965G>A) in the general population?

ATL2 p.Arg322Gln (c.965G>A) is rare (popmax 0.49%, nfe) (gnomAD).

What do computational predictors say about ATL2 p.Arg322Gln (c.965G>A)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

ATL2 p.Arg322Gln

c.965G>A · rs61754249 · VCV2650839

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.49%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -5.84	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 3.3	GERP -0.019, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 81 kb · p 0.18 · regional, not allelic
Overall
CADD	23.3	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 0.49% European (non-Finnish) · 5,779/1,179,374 alleles

Filtering AF 0.479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.475%

Overall 0.5% 8,057/1,611,176 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.95%	34
European (non-Finnish)grpmax	0.49%	204
Remaining individualsnot grpmax-eligible	0.359%	279
Ashkenazi Jewishnot grpmax-eligible	0.227%	441
Admixed American	0.0873%	1,146
African / African-American	0.0628%	1,593
South Asian	0.0374%	2,670
Middle Eastern	0.0165%	6,048
East Asian	0.00447%	22,387

Finnish 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: ATL2
Protein: p.Arg322Gln
Coding: c.965G>A
MANE Select: NM_001135673
dbSNP: rs61754249
Type: single nucleotide variant
Location: chr2:38309485 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.36
Residue 322: the gb1/rhd3-type g domain

Full ATL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATL2 p.Gly365= Benign ★★ same type
ATL2 p.Ala100Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala227Gly Uncertain significance ★ ⚠ same type
ATL2 p.Ala28Gly Uncertain significance ★ ⚠ same type
ATL2 p.Ala2Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala388Ser Uncertain significance ★ ⚠ same type
ATL2 p.Ala388Val Uncertain significance ★ ⚠ same type
ATL2 p.Ala425Val 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/atl2-p-arg322gln (accessed [today's date]).

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