Is ALK p.Asp70Glu (c.210C>G) pathogenic?

ALK p.Asp70Glu (c.210C>G) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-25). AlphaMissense: likely benign (0.1602); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Asp70Glu (c.210C>G)?

ALK p.Asp70Glu (c.210C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Asp70Glu (c.210C>G) in the general population?

ALK p.Asp70Glu (c.210C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALK p.Asp70Glu (c.210C>G)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

ALK p.Asp70Glu

c.210C>G · VCV3524189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.83	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 2.4	GERP -0.032, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 670 kb · p 0.12 · regional, not allelic
Overall
CADD	16.35	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALK
Protein: p.Asp70Glu
Coding: c.210C>G
MANE Select: NM_004304
Type: single nucleotide variant
Location: chr2:29920450 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 70: the 'heparin-binding region' region

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

Similar variants

ALK p.Asp70= Likely benign ★★ same residue
ALK p.Asp70Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK p.Asp70Gly Uncertain significance ★ ⚠ same residue
ALK p.Asp70Ala 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

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-asp70glu (accessed [today's date]).

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