Is ALK p.Ala892= (c.2676C>T) pathogenic?

ALK p.Ala892= (c.2676C>T) is classified Benign/Likely benign in ALK (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). Rare (popmax 0.564%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ala892= (c.2676C>T)?

ALK p.Ala892= (c.2676C>T) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ala892= (c.2676C>T) in the general population?

ALK p.Ala892= (c.2676C>T) is rare (popmax 0.564%, eas) (gnomAD).

ALK p.Ala892=

c.2676C>T · rs138668699 · VCV239811

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.564%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.7	GERP -3.5, phastCons 0.98
Overall
CADD	8.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.564% East Asian · 250/44,360 alleles

Filtering AF 0.506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.484%

Overall 0.117% 1,866/1,601,550 alleles · rare exomes 1,639/1,458,972 · genomes 227/142,578 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.25%	80
Ashkenazi Jewishnot grpmax-eligible	0.786%	127
East Asiangrpmax	0.564%	177
Remaining individualsnot grpmax-eligible	0.159%	628
Middle Eastern	0.05%	2,002
South Asian	0.0375%	2,669
European (non-Finnish)	0.0372%	2,687
African / African-American	0.028%	3,576
Admixed American	0.0278%	3,596

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala892=
Coding: c.2676C>T
MANE Select: NM_004304
dbSNP: rs138668699
Type: single nucleotide variant
Location: chr2:29229023 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB
Residue 892: a β-strand

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.Ala892Thr Uncertain significance ★★ ⚠ same residue
ALK p.Ala892Asp Uncertain significance ★ ⚠ same residue
ALK p.Ala892fs 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-ala892 (accessed [today's date]).

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