Is ALK p.Ser785= (c.2355T>C) pathogenic?

ALK p.Ser785= (c.2355T>C) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). Very rare (popmax 6.2e-05%); Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Ser785= (c.2355T>C)?

ALK p.Ser785= (c.2355T>C) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ser785= (c.2355T>C) in the general population?

ALK p.Ser785= (c.2355T>C) is very rare (popmax 6.2e-05%) (gnomAD).

ALK p.Ser785=

c.2355T>C · VCV4723247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.4	GERP -4.2
Overall
CADD	2.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,650 alleles · very rare exomes 0/1,461,558 · genomes 1/152,092 · joint denominator

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.Ser785=
Coding: c.2355T>C
MANE Select: NM_004304
Type: single nucleotide variant
Location: chr2:29239680 (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

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

Similar variants

ALK p.Ser785Asn Uncertain significance ★★ ⚠ same residue
ALK p.Ser785Gly Uncertain significance ★★ ⚠ same residue
ALK p.Ser785Ile Uncertain significance ★★ ⚠ same residue
ALK p.Ser785Arg Uncertain significance ★ ⚠ same residue
ALK p.Ser785Thr 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

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-ser785 (accessed [today's date]).

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