Is ULK2 p.Ala896Val (c.2687C>T) pathogenic?

ULK2 p.Ala896Val (c.2687C>T) is classified Uncertain significance in ULK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.5316); Very rare (popmax 0.00329%, sas).

How common is ULK2 p.Ala896Val (c.2687C>T) in the general population?

ULK2 p.Ala896Val (c.2687C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ULK2 p.Ala896Val (c.2687C>T)?

AlphaMissense predicts ambiguous (score 0.5316) — an in-silico prediction, not a clinical call.

ULK2 p.Ala896Val

c.2687C>T · VCV3977515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5316	ambiguous
REVEL	0.273	benign-leaning
SaProt	LLR -8.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 50 kb · p 0.065 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00329% South Asian · 3/91,058 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00217% 35/1,613,714 alleles · very rare exomes 32/1,461,706 · genomes 3/152,008 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
European (non-Finnish)	0.00254%	39,332
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00134%	74,850

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: ULK2
Protein: p.Ala896Val
Coding: c.2687C>T
MANE Select: NM_014683
Type: single nucleotide variant
Location: chr17:19781057 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 5 PDB
Residue 896: the 'ctd-like region' region

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

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-ala896val (accessed [today's date]).

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