Is ALK p.Arg1061Gln (c.3182G>A) pathogenic?

ALK p.Arg1061Gln (c.3182G>A) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1398); Ultra-rare (popmax 0.034%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Arg1061Gln (c.3182G>A)?

ALK p.Arg1061Gln (c.3182G>A) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Arg1061Gln (c.3182G>A) in the general population?

ALK p.Arg1061Gln (c.3182G>A) is ultra-rare (popmax 0.034%, sas) (gnomAD).

What do computational predictors say about ALK p.Arg1061Gln (c.3182G>A)?

AlphaMissense predicts likely benign (score 0.1398) — an in-silico prediction, not a clinical call.

ALK p.Arg1061Gln

c.3182G>A · rs72852032 · VCV133470

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1398 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1398	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.57	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.039 · regional, not allelic
Overall
CADD	35.0	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 0.034% South Asian · 31/91,058 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00961% 155/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,937
Middle Eastern	0.0166%	6,036
Remaining individualsnot grpmax-eligible	0.0096%	10,416
European (non-Finnish)	0.00949%	10,536
East Asian	0.00446%	22,430
African / African-American	0.004%	25,007

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: ALK
Protein: p.Arg1061Gln
Coding: c.3182G>A
MANE Select: NM_004304
dbSNP: rs72852032
Type: single nucleotide variant
Location: chr2:29223519 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuroblastoma, susceptibility to, 3

Similar variants

ALK p.Arg1061= Uncertain significance ★★ same residue
ALK p.Arg1061Trp Uncertain significance ★★ ⚠ same residue
ALK p.Arg1275Gln Pathogenic ★★ same condition
ALK c.1154+5G>A Uncertain significance ★★ same condition
ALK c.1155-3C>T Uncertain significance ★★ same condition
ALK c.1282+3A>G Uncertain significance ★★ same condition
ALK c.1414+1G>A Uncertain significance ★★ same condition
ALK c.1414+3G>A Uncertain significance ★★ same condition

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/alk-p-arg1061gln (accessed [today's date]).

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