Is CUL4A p.Glu201Lys (c.601G>A) pathogenic?

CUL4A p.Glu201Lys (c.601G>A) is classified Uncertain significance in CUL4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.2194); Very rare (popmax 0.00667%, afr).

How common is CUL4A p.Glu201Lys (c.601G>A) in the general population?

CUL4A p.Glu201Lys (c.601G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about CUL4A p.Glu201Lys (c.601G>A)?

AlphaMissense predicts likely benign (score 0.2194) — an in-silico prediction, not a clinical call.

CUL4A p.Glu201Lys

c.601G>A · VCV3498629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2194 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2194	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 0.93
Regional constraint	o/e 0.97	unconstrained · MANE · 4,451 bp · p 0.74 · regional, not allelic
Overall
CADD	22.4	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 0.00667% African / African-American · 5/74,942 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00322% 52/1,613,904 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,988
European (non-Finnish)	0.00373%	26,819
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,008

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: CUL4A
Protein: p.Glu201Lys
Coding: c.601G>A
MANE Select: NM_001008895
Type: single nucleotide variant
Location: chr13:113233265 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.26 · 20 PDB
Residue 201: an α-helix

Full CUL4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUL4A p.Ala13Pro Uncertain significance ★ ⚠ same type
CUL4A p.Ala208Val Uncertain significance ★ ⚠ same type
CUL4A p.Ala486Thr Uncertain significance ★ ⚠ same type
CUL4A p.Arg144Gly Uncertain significance ★ ⚠ same type
CUL4A p.Arg385Gln Uncertain significance ★ ⚠ same type
CUL4A p.Arg49Gln Uncertain significance ★ ⚠ same type
CUL4A p.Arg80Lys Uncertain significance ★ ⚠ same type
CUL4A p.Asn603Ser Uncertain significance ★ ⚠ 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/cul4a-p-glu201lys (accessed [today's date]).

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