Is ULK1 p.Arg697Cys (c.2089C>T) pathogenic?

ULK1 p.Arg697Cys (c.2089C>T) is classified Uncertain significance in ULK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.1792); Very rare (popmax 0.00729%, nfe).

How common is ULK1 p.Arg697Cys (c.2089C>T) in the general population?

ULK1 p.Arg697Cys (c.2089C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about ULK1 p.Arg697Cys (c.2089C>T)?

AlphaMissense predicts likely benign (score 0.1792) — an in-silico prediction, not a clinical call.

ULK1 p.Arg697Cys

c.2089C>T · rs759685631 · VCV2371820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1792	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -7.04	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 6,947 bp · p 0.16 · regional, not allelic
Overall
CADD	32.0	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 0.00729% European (non-Finnish) · 86/1,179,032 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00615% 99/1,610,190 alleles · very rare exomes 91/1,458,952 · genomes 8/151,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,710
East Asian	0.00447%	22,370
South Asian	0.0044%	22,727
African / African-American	0.00404%	24,769
Finnishnot grpmax-eligible	0.0032%	31,259
Admixed American	0.00167%	59,818
Remaining individualsnot grpmax-eligible	0.0016%	62,350

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.Arg697Cys
Coding: c.2089C>T
MANE Select: NM_003565
dbSNP: rs759685631
Type: single nucleotide variant
Location: chr12:131916969 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 19 PDB

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-arg697cys (accessed [today's date]).

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