Is ULK3 p.Ser147Phe (c.440C>T) pathogenic?

ULK3 p.Ser147Phe (c.440C>T) is classified Uncertain significance in ULK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: ambiguous (0.4178); Very rare (popmax 0.00331%, nfe).

How common is ULK3 p.Ser147Phe (c.440C>T) in the general population?

ULK3 p.Ser147Phe (c.440C>T) is very rare (popmax 0.00331%, nfe) (gnomAD).

What do computational predictors say about ULK3 p.Ser147Phe (c.440C>T)?

AlphaMissense predicts ambiguous (score 0.4178) — an in-silico prediction, not a clinical call.

ULK3 p.Ser147Phe

c.440C>T · VCV3813432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4178 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4178	ambiguous
REVEL	0.169	moderately benign-leaning
SaProt	LLR -12.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 5,874 bp · p 0.0054 · regional, not allelic
Overall
CADD	26.1	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 0.00331% European (non-Finnish) · 39/1,179,856 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00254% 41/1,613,784 alleles · very rare exomes 39/1,461,600 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,253
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Ser147Phe
Coding: c.440C>T
MANE Select: NM_001099436
Type: single nucleotide variant
Location: chr15:74841434 (GRCh38)
Gene constraint: LOEUF 1.161 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 3 PDB
Residue 147: the protein kinase domain; a β-strand

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-ser147phe (accessed [today's date]).

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