Is ULK1 p.Arg34Cys (c.100C>T) pathogenic?

ULK1 p.Arg34Cys (c.100C>T) is classified Uncertain significance in ULK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.5412); Ultra-rare (popmax 0.0408%, sas).

How common is ULK1 p.Arg34Cys (c.100C>T) in the general population?

ULK1 p.Arg34Cys (c.100C>T) is ultra-rare (popmax 0.0408%, sas) (gnomAD).

What do computational predictors say about ULK1 p.Arg34Cys (c.100C>T)?

AlphaMissense predicts ambiguous (score 0.5412) — an in-silico prediction, not a clinical call.

ULK1 p.Arg34Cys

c.100C>T · rs546631115 · VCV3186316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5412 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0408%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5412	ambiguous
REVEL	0.271	benign-leaning
SaProt	LLR -13.10	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 0.31, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 15 kb · p 2e-08 · regional, not allelic
Overall
CADD	31.0	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 0.0408% South Asian · 35/85,734 alleles

Filtering AF 0.0302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0264%

Overall 0.00237% 37/1,560,250 alleles · ultra-rare exomes 35/1,408,992 · genomes 2/151,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0408%	2,450
East Asian	0.00238%	41,952
Finnishnot grpmax-eligible	0.00203%	49,304

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: ULK1
Protein: p.Arg34Cys
Coding: c.100C>T
MANE Select: NM_003565
dbSNP: rs546631115
Type: single nucleotide variant
Location: chr12:131895101 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 19 PDB
Residue 34: the protein kinase domain; a β-strand

Full ULK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ULK1 p.Thr660Met Uncertain significance ★★ ⚠ same type
ULK1 p.Ala923= Benign ★★ same type
ULK1 p.Arg966= Benign ★★ same type
ULK1 p.Gly757= Benign ★★ same type
ULK1 p.Leu596= Benign ★★ same type
ULK1 p.Leu926= Benign ★★ same type
ULK1 p.Leu957= Benign/Likely benign ★★ same type
ULK1 p.Pro574= Benign/Likely 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/ulk1-p-arg34cys (accessed [today's date]).

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