Is ULK4 p.Leu112Phe (c.334C>T) pathogenic?

ULK4 p.Leu112Phe (c.334C>T) is classified Uncertain significance in ULK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: ambiguous (0.5234); Absent from gnomAD v4.1.

How common is ULK4 p.Leu112Phe (c.334C>T) in the general population?

ULK4 p.Leu112Phe (c.334C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ULK4 p.Leu112Phe (c.334C>T)?

AlphaMissense predicts ambiguous (score 0.5234) — an in-silico prediction, not a clinical call.

ULK4 p.Leu112Phe

c.334C>T · rs2471269906 · VCV2267311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5234 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5234	ambiguous
REVEL	0.609	indeterminate
SaProt	LLR -11.62	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 708 kb · p 0.038 · regional, not allelic
Overall
CADD	27.6	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: ULK4
Protein: p.Leu112Phe
Coding: c.334C>T
MANE Select: NM_017886
dbSNP: rs2471269906
Type: single nucleotide variant
Location: chr3:41935845 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 2 PDB
Residue 112: the protein kinase domain; an α-helix

Full ULK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ULK4 c.1183-8C>A Benign ★★ same type
ULK4 c.1288-9A>T Benign ★★ same type
ULK4 c.1349-5C>G Benign ★★ same type
ULK4 c.1577+10G>A Benign ★★ same type
ULK4 c.803+3A>C Benign ★★ same type
ULK4 p.Ala542Thr Benign ★★ same type
ULK4 p.Asn139Lys Likely benign ★★ ⚠ same type
ULK4 p.Ile224Val Benign ★★ 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/ulk4-p-leu112phe (accessed [today's date]).

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