Is ALK p.Ser1483Pro (c.4447T>C) pathogenic?

ALK p.Ser1483Pro (c.4447T>C) is classified Benign in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.0897); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with ALK p.Ser1483Pro (c.4447T>C)?

ALK p.Ser1483Pro (c.4447T>C) is associated with ovarian cancer (ClinVar).

How common is ALK p.Ser1483Pro (c.4447T>C) in the general population?

ALK p.Ser1483Pro (c.4447T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALK p.Ser1483Pro (c.4447T>C)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

ALK p.Ser1483Pro

c.4447T>C · rs2148138302 · VCV2445317

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -3.6, phastCons 0.006
Regional constraint	o/e 1.10	unconstrained · MANE · 4,393 bp · p 0.054 · regional, not allelic
Overall
CADD	16.01	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALK
Protein: p.Ser1483Pro
Coding: c.4447T>C
MANE Select: NM_004304
dbSNP: rs2148138302
Type: single nucleotide variant
Location: chr2:29193640 (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

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALK p.Ala371Thr Benign/Likely benign ★★ same condition
ALK p.Lys134Asn Likely pathogenic ★ ⚠ same condition
ALK p.Ala613Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
ALK p.Arg291His Conflicting classifications of pathogenicity ★ ⚠ same condition
ALK p.Gln459Glu Conflicting classifications of pathogenicity ★ ⚠ same condition
ALK p.His1528Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
ALK p.Leu1404Val Conflicting classifications of pathogenicity ★ ⚠ same condition
ALK p.Leu550Phe Conflicting classifications of pathogenicity ★ ⚠ 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-ser1483pro (accessed [today's date]).

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