Is ULK2 p.Ala99Val (c.296C>T) pathogenic?

ULK2 p.Ala99Val (c.296C>T) is classified Likely benign in ULK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1659); Very rare (popmax 0.00898%, eas).

How common is ULK2 p.Ala99Val (c.296C>T) in the general population?

ULK2 p.Ala99Val (c.296C>T) is very rare (popmax 0.00898%, eas) (gnomAD).

What do computational predictors say about ULK2 p.Ala99Val (c.296C>T)?

AlphaMissense predicts likely benign (score 0.1659) — an in-silico prediction, not a clinical call.

ULK2 p.Ala99Val

c.296C>T · rs756982575 · VCV2557496

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1659	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 0.69, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 41 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	21.3	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 0.00898% East Asian · 4/44,568 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00199% 32/1,605,490 alleles · very rare exomes 29/1,453,392 · genomes 3/152,098 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00898%	11,142
South Asian	0.00337%	29,654
Remaining individualsnot grpmax-eligible	0.00322%	31,090
African / African-American	0.00268%	37,298
European (non-Finnish)	0.0017%	58,825
Finnishnot grpmax-eligible	0.00157%	63,876

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.Ala99Val
Coding: c.296C>T
MANE Select: NM_014683
dbSNP: rs756982575
Type: single nucleotide variant
Location: chr17:19846910 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.32 · 5 PDB
Residue 99: the protein kinase domain; an α-helix

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-ala99val (accessed [today's date]).

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