Is ULK4 p.Cys802Arg (c.2404T>C) pathogenic?

ULK4 p.Cys802Arg (c.2404T>C) is classified Uncertain significance in ULK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.9627); Ultra-rare (popmax 0.035%, amr).

How common is ULK4 p.Cys802Arg (c.2404T>C) in the general population?

ULK4 p.Cys802Arg (c.2404T>C) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about ULK4 p.Cys802Arg (c.2404T>C)?

AlphaMissense predicts likely pathogenic (score 0.9627) — an in-silico prediction, not a clinical call.

ULK4 p.Cys802Arg

c.2404T>C · VCV3813438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9627 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9627	likely pathogenic · top 2% in ULK4
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 708 kb · p 0.038 · regional, not allelic
Overall
CADD	24.9	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 0.035% Admixed American · 21/59,996 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00136% 22/1,614,012 alleles · ultra-rare exomes 20/1,461,828 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Cys802Arg
Coding: c.2404T>C
MANE Select: NM_017886
Type: single nucleotide variant
Location: chr3:41717779 (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

Similar variants

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
ULK4 p.Ala542Thr Benign ★★ same type
ULK4 p.Asn139Lys Likely benign ★★ ⚠ same type
ULK4 p.Ile224Val 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-cys802arg (accessed [today's date]).

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