Is ULK3 p.Ser462Leu (c.1385C>T) pathogenic?

ULK3 p.Ser462Leu (c.1385C>T) is classified Uncertain significance in ULK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0809); Very rare (popmax 0.00446%, eas).

How common is ULK3 p.Ser462Leu (c.1385C>T) in the general population?

ULK3 p.Ser462Leu (c.1385C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about ULK3 p.Ser462Leu (c.1385C>T)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

ULK3 p.Ser462Leu

c.1385C>T · rs769848635 · VCV2479642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.60	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 -0.023	GERP -4
Regional constraint	o/e 0.89	unconstrained · MANE · 5,874 bp · p 0.0054 · regional, not allelic
Overall
CADD	13.64	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 0.00446% East Asian · 2/44,842 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00291% 47/1,612,930 alleles · very rare exomes 44/1,460,802 · genomes 3/152,128 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,421
European (non-Finnish)	0.00348%	28,769
Remaining individualsnot grpmax-eligible	0.0032%	31,219
Finnishnot grpmax-eligible	0.00156%	63,962
African / African-American	0.00134%	74,886

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.Ser462Leu
Coding: c.1385C>T
MANE Select: NM_001099436
dbSNP: rs769848635
Type: single nucleotide variant
Location: chr15:74837386 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 3 PDB

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.Ala114Val Uncertain significance ★ ⚠ 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

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-ser462leu (accessed [today's date]).

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