Is ALK p.Ala87Asp (c.260C>A) pathogenic?

ALK p.Ala87Asp (c.260C>A) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-15). AlphaMissense: likely pathogenic (0.7663); Very rare (popmax 6.34e-05%); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ala87Asp (c.260C>A)?

ALK p.Ala87Asp (c.260C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Ala87Asp (c.260C>A) in the general population?

ALK p.Ala87Asp (c.260C>A) is very rare (popmax 6.34e-05%) (gnomAD).

What do computational predictors say about ALK p.Ala87Asp (c.260C>A)?

AlphaMissense predicts likely pathogenic (score 0.7663) — an in-silico prediction, not a clinical call.

ALK p.Ala87Asp

c.260C>A · rs2148443609 · VCV1793770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.34e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7663	likely pathogenic
REVEL	0.227	benign-leaning
SaProt	LLR -12.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.85, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 670 kb · p 0.12 · regional, not allelic
Overall
CADD	19.83	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 6.34e-05%

Overall 6.34e-05% 1/1,576,190 alleles · very rare exomes 1/1,423,856 · genomes 0/152,334 · 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.Ala87Asp
Coding: c.260C>A
MANE Select: NM_004304
dbSNP: rs2148443609
Type: single nucleotide variant
Location: chr2:29920400 (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

Similar variants

ALK p.Ala87Val Uncertain significance ★★ ⚠ same residue
ALK p.Ala87= Likely benign ★★ same residue
ALK p.Ala87Thr 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

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-ala87asp (accessed [today's date]).

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