Is ALK p.Ser711= (c.2133C>T) pathogenic?

ALK p.Ser711= (c.2133C>T) is classified Benign in ALK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-30). Low-frequency (popmax 2.2%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Ser711= (c.2133C>T)?

ALK p.Ser711= (c.2133C>T) is associated with hereditary neoplastic syndrome, neuroblastoma, susceptibility to, 3 (ClinVar).

How common is ALK p.Ser711= (c.2133C>T) in the general population?

ALK p.Ser711= (c.2133C>T) is low-frequency (popmax 2.2%, afr) (gnomAD).

ALK p.Ser711=

c.2133C>T · rs77102810 · VCV239800

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.2%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -4.7, phastCons 0.33
Overall
CADD	7.985	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.2% African / African-American · 1,648/75,044 alleles

Filtering AF 2.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.07%

Overall 0.119% 1,917/1,614,072 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.2%	46
Remaining individualsnot grpmax-eligible	0.123%	812
Admixed American	0.112%	896
South Asian	0.0923%	1,084
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.00314%	31,891

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.Ser711=
Coding: c.2133C>T
MANE Select: NM_004304
dbSNP: rs77102810
Type: single nucleotide variant
Location: chr2:29251176 (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

Also linked: neuroblastoma, susceptibility to, 3

Similar variants

ALK p.Ser711Arg Uncertain significance ★★ ⚠ same residue
ALK p.Ser711Asn Uncertain significance ★★ ⚠ same residue
ALK p.Ser711Gly 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-ser711 (accessed [today's date]).

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