Is ULK4 p.Val533= (c.1599A>G) pathogenic?

ULK4 p.Val533= (c.1599A>G) is classified Benign in ULK4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-29). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele.

ULK4 p.Val533=

Q: How common is ULK4 p.Val533= (c.1599A>G) in the general population?

ULK4 p.Val533= (c.1599A>G) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1599A>G · rs1716687 · VCV403585

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -0.049, phastCons 1
Overall
CADD	8.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,881/44,882 alleles

Filtering AF 99.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.6%

Overall 98.5% 1,586,593/1,611,248 alleles · common exomes 1,445,208/1,458,954 · genomes 141,385/152,294 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
East Asiangrpmax	100%	1
Finnishnot grpmax-eligible	99.9%	1
South Asian	99.9%	1
European (non-Finnish)	99.8%	1
Ashkenazi Jewishnot grpmax-eligible	98.1%	1
Remaining individualsnot grpmax-eligible	97.8%	1
Admixed American	97.6%	1
Middle Eastern	94.9%	1
African / African-American	75.1%	1

Amish 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.Val533=
Coding: c.1599A>G
MANE Select: NM_017886
dbSNP: rs1716687
Type: single nucleotide variant
Location: chr3:41883931 (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-val533 (accessed [today's date]).

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