Is ULK3 p.Ala114Val (c.341C>T) pathogenic?

ULK3 p.Ala114Val (c.341C>T) is classified Uncertain significance in ULK3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-28). AlphaMissense: likely benign (0.1214); Ultra-rare (popmax 0.0401%, eas).

How common is ULK3 p.Ala114Val (c.341C>T) in the general population?

ULK3 p.Ala114Val (c.341C>T) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

What do computational predictors say about ULK3 p.Ala114Val (c.341C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

ULK3 p.Ala114Val

c.341C>T · rs775347115 · VCV3186360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.29	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 5,874 bp · p 0.0054 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,904 alleles

Filtering AF 0.0258% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.00366% 59/1,613,750 alleles · ultra-rare exomes 55/1,461,556 · genomes 4/152,194 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,495
African / African-American	0.004%	24,971
European (non-Finnish)	0.00297%	33,711
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: ULK3
Protein: p.Ala114Val
Coding: c.341C>T
MANE Select: NM_001099436
dbSNP: rs775347115
Type: single nucleotide variant
Location: chr15:74842098 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 3 PDB
Residue 114: the protein kinase domain; an α-helix

Full ULK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ULK3 p.Arg101His Benign ★★ same type
ULK3 p.Pro177= Benign ★★ same type
ULK3 p.Ser468= Benign ★★ same type
ULK3 p.Ala192Thr Uncertain significance ★ ⚠ same type
ULK3 p.Ala26Thr Uncertain significance ★ ⚠ same type
ULK3 p.Ala286Val Uncertain significance ★ ⚠ same type
ULK3 p.Ala303Thr Uncertain significance ★ ⚠ same type
ULK3 p.Ala378Thr 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/ulk3-p-ala114val (accessed [today's date]).

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