Is ULK4 p.Arg862Ter (c.2584C>T) pathogenic?

ULK4 p.Arg862Ter (c.2584C>T) is classified Likely benign in ULK4 (ClinVar, Single submitter, 2 submitters; last evaluated 2016-07-14). Rare (popmax 0.445%, nfe); Associated with Moderate intellectual disability.

What condition is associated with ULK4 p.Arg862Ter (c.2584C>T)?

ULK4 p.Arg862Ter (c.2584C>T) is associated with Moderate intellectual disability (ClinVar).

How common is ULK4 p.Arg862Ter (c.2584C>T) in the general population?

ULK4 p.Arg862Ter (c.2584C>T) is rare (popmax 0.445%, nfe) (gnomAD).

ULK4 p.Arg862Ter

c.2584C>T · rs199884004 · VCV224081

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.445%, nfe)

Conditions

Moderate intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 25 of 37
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Pangolin	Δ0.38	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.445% European (non-Finnish) · 5,255/1,179,958 alleles

Filtering AF 0.435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.431%

Overall 0.379% 6,119/1,613,740 alleles · rare exomes 5,711/1,461,492 · genomes 408/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.525%	191
European (non-Finnish)grpmax	0.445%	225
Remaining individualsnot grpmax-eligible	0.341%	293
Ashkenazi Jewishnot grpmax-eligible	0.193%	519
South Asian	0.178%	562
African / African-American	0.0893%	1,119
Middle Eastern	0.0682%	1,466
East Asian	0.029%	3,451
Admixed American	0.02%	5,000

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ULK4
Protein: p.Arg862Ter
Coding: c.2584C>T
MANE Select: NM_017886
dbSNP: rs199884004
Type: single nucleotide variant
Location: chr3:41715287 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 2 PDB

Full ULK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Moderate intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ULK4 p.Arg862Gln Uncertain significance ★ ⚠ same residue
ULK4 p.Val686Ile Likely benign ★★ same condition
ULK4 p.Val963Met Likely benign ★ same condition
ULK4 c.1183-8C>A Benign ★★ same type
ULK4 c.1288-9A>T Benign ★★ same type
ULK4 c.1349-5C>G Benign ★★ same type
ULK4 c.1577+10G>A Benign ★★ same type
ULK4 c.803+3A>C 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/ulk4-p-arg862ter (accessed [today's date]).

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