Is ULK1 p.Val883Ala (c.2648T>C) pathogenic?

ULK1 p.Val883Ala (c.2648T>C) is classified Uncertain significance in ULK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.4971); Very rare (popmax 0.00371%, nfe).

How common is ULK1 p.Val883Ala (c.2648T>C) in the general population?

ULK1 p.Val883Ala (c.2648T>C) is very rare (popmax 0.00371%, nfe) (gnomAD).

What do computational predictors say about ULK1 p.Val883Ala (c.2648T>C)?

AlphaMissense predicts ambiguous (score 0.4971) — an in-silico prediction, not a clinical call.

ULK1 p.Val883Ala

c.2648T>C · VCV4195897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00371%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4971	ambiguous
REVEL	0.3	indeterminate
SaProt	LLR -5.26	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 6,947 bp · p 0.16 · regional, not allelic
Overall
CADD	25.7	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 0.00371% European (non-Finnish) · 37/997,168 alleles

Filtering AF 0.00274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.00291% 38/1,306,564 alleles · very rare exomes 34/1,176,990 · genomes 4/129,574 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00371%	26,950
Remaining individualsnot grpmax-eligible	0.00225%	44,380

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.Val883Ala
Coding: c.2648T>C
MANE Select: NM_003565
Type: single nucleotide variant
Location: chr12:131919348 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99 · 19 PDB
Residue 883: the 'c-terminal domain; mediates interaction with sesn2' region

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-val883ala (accessed [today's date]).

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