Is ULK4 p.Phe950Ser (c.2849T>C) pathogenic?

ULK4 p.Phe950Ser (c.2849T>C) is classified Uncertain significance in ULK4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.4217); Rare (popmax 0.257%, afr).

How common is ULK4 p.Phe950Ser (c.2849T>C) in the general population?

ULK4 p.Phe950Ser (c.2849T>C) is rare (popmax 0.257%, afr) (gnomAD).

What do computational predictors say about ULK4 p.Phe950Ser (c.2849T>C)?

AlphaMissense predicts ambiguous (score 0.4217) — an in-silico prediction, not a clinical call.

ULK4 p.Phe950Ser

c.2849T>C · rs201806676 · VCV3048584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4217 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.257%, afr)

Computational evidence

Protein change
AlphaMissense	0.4217	ambiguous
REVEL	0.309	indeterminate
SaProt	LLR -3.35	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 0.81, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 708 kb · p 0.038 · regional, not allelic
Overall
CADD	23.7	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 0.257% African / African-American · 193/75,000 alleles

Filtering AF 0.228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.0152% 245/1,614,002 alleles · rare exomes 118/1,461,752 · genomes 127/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.257%	389
Admixed American	0.035%	2,857
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.00161%	62,104
South Asian	0.0011%	91,062

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.Phe950Ser
Coding: c.2849T>C
MANE Select: NM_017886
dbSNP: rs201806676
Type: single nucleotide variant
Location: chr3:41681637 (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-phe950ser (accessed [today's date]).

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