Is ULK2 p.Ala172Ser (c.514G>T) pathogenic?

ULK2 p.Ala172Ser (c.514G>T) is classified Uncertain significance in ULK2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6633); Absent from gnomAD v4.1; Associated with prostate cancer.

What condition is associated with ULK2 p.Ala172Ser (c.514G>T)?

ULK2 p.Ala172Ser (c.514G>T) is associated with prostate cancer (ClinVar).

How common is ULK2 p.Ala172Ser (c.514G>T) in the general population?

ULK2 p.Ala172Ser (c.514G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ULK2 p.Ala172Ser (c.514G>T)?

AlphaMissense predicts likely pathogenic (score 0.6633) — an in-silico prediction, not a clinical call.

ULK2 p.Ala172Ser

c.514G>T · rs193921089 · VCV161681

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6633 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

prostate cancer

Computational evidence

Protein change
AlphaMissense	0.6633	likely pathogenic
REVEL	0.332	indeterminate
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 41 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	26.6	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: ULK2
Protein: p.Ala172Ser
Coding: c.514G>T
MANE Select: NM_014683
dbSNP: rs193921089
Type: single nucleotide variant
Location: chr17:19845333 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 5 PDB
Residue 172: the protein kinase domain; an α-helix

Full ULK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

ULK2 p.Arg881Gln Benign ★★ same type
ULK2 p.Gly5= Benign ★★ same type
ULK2 p.Lys539= Benign ★★ same type
ULK2 p.Tyr795= Benign ★★ same type
ULK2 p.His578Arg Likely pathogenic ★ ⚠ same type
ULK2 p.Ala1034Thr Uncertain significance ★ ⚠ same type
ULK2 p.Ala264Glu Uncertain significance ★ ⚠ same type
ULK2 p.Ala264Val Uncertain significance ★ ⚠ same type

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/ulk2-p-ala172ser (accessed [today's date]).

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