Is ALK p.Glu310Asp (c.930G>T) pathogenic?

ALK p.Glu310Asp (c.930G>T) is classified Conflicting classifications of pathogenicity in ALK (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.0936); Ultra-rare (popmax 0.015%, amr); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Glu310Asp (c.930G>T)?

ALK p.Glu310Asp (c.930G>T) is associated with neuroblastoma, susceptibility to, 3, hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Glu310Asp (c.930G>T) in the general population?

ALK p.Glu310Asp (c.930G>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about ALK p.Glu310Asp (c.930G>T)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

ALK p.Glu310Asp

c.930G>T · rs367712624 · VCV335709

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.63	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 -3.9	GERP -4.7
Regional constraint	o/e 1.05	unconstrained · MANE · 670 kb · p 0.12 · regional, not allelic
Overall
CADD	3.192	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 0.015% Admixed American · 9/60,026 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00254% 41/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,670
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.00229%	43,702

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.Glu310Asp
Coding: c.930G>T
MANE Select: NM_004304
dbSNP: rs367712624
Type: single nucleotide variant
Location: chr2:29694872 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 310: the mam 1 domain

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

Disease context

neuroblastoma, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

ALK p.Glu310= Likely benign ★★ same residue
ALK p.Glu310Gln Uncertain significance ★ ⚠ same residue
ALK p.Glu310Ala Likely benign ★ 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

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-glu310asp (accessed [today's date]).

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