Is CDC5L p.Lys380= (c.1140A>G) pathogenic?

CDC5L p.Lys380= (c.1140A>G) is classified Likely benign in CDC5L (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-06). Ultra-rare (popmax 0.0999%, afr); Associated with CDC5L-related disorder.

What condition is associated with CDC5L p.Lys380= (c.1140A>G)?

CDC5L p.Lys380= (c.1140A>G) is associated with CDC5L-related disorder (ClinVar).

How common is CDC5L p.Lys380= (c.1140A>G) in the general population?

CDC5L p.Lys380= (c.1140A>G) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

CDC5L p.Lys380=

c.1140A>G · rs144752067 · VCV3048800

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Conditions

CDC5L-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.4, phastCons 1
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0999% African / African-American · 75/75,054 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.075%

Overall 0.00527% 85/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00333%	30,013

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: CDC5L
Protein: p.Lys380=
Coding: c.1140A>G
MANE Select: NM_001253
dbSNP: rs144752067
Type: single nucleotide variant
Location: chr6:44419496 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 41 PDB
Residue 380: the 'interaction with ppp1r8' region

Full CDC5L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDC5L-related disorder

Similar variants

CDC5L p.Arg426Gln Uncertain significance ★ ⚠ same condition
CDC5L p.Met582Arg Uncertain significance ★ ⚠ same condition
CDC5L p.Arg49= Uncertain significance same condition
CDC5L c.904-10G>A Likely benign same condition
CDC5L c.-2A>G Likely benign same condition
CDC5L c.-7C>T Likely benign same condition
CDC5L p.Ala22= Likely benign same condition
CDC5L p.Ala305= Benign same condition

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/cdc5l-p-lys380 (accessed [today's date]).

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