Is ALK p.Pro157= (c.471C>T) pathogenic?

ALK p.Pro157= (c.471C>T) is classified Likely benign in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-31). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with ALK p.Pro157= (c.471C>T)?

ALK p.Pro157= (c.471C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is ALK p.Pro157= (c.471C>T) in the general population?

ALK p.Pro157= (c.471C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ALK p.Pro157=

c.471C>T · VCV4870491

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 1.3	GERP -0.09, phastCons 1
Overall
CADD	4.446	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.2e-05% 1/1,613,502 alleles · very rare exomes 1/1,461,156 · genomes 0/152,346 · 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.Pro157=
Coding: c.471C>T
MANE Select: NM_004304
Type: single nucleotide variant
Location: chr2:29920189 (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.Pro157Thr Uncertain significance ★★ ⚠ same residue
ALK p.Pro157Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK p.Pro157Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ALK p.Pro157Ala Likely benign ★ same residue
ALK p.Pro157Arg 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-pro157 (accessed [today's date]).

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