Is CDC5L p.Leu720Phe (c.2160G>C) pathogenic?

CDC5L p.Leu720Phe (c.2160G>C) is classified Likely benign in CDC5L (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.4791); Low-frequency (popmax 1.28%, afr).

How common is CDC5L p.Leu720Phe (c.2160G>C) in the general population?

CDC5L p.Leu720Phe (c.2160G>C) is low-frequency (popmax 1.28%, afr) (gnomAD).

What do computational predictors say about CDC5L p.Leu720Phe (c.2160G>C)?

AlphaMissense predicts ambiguous (score 0.4791) — an in-silico prediction, not a clinical call.

CDC5L p.Leu720Phe

c.2160G>C · rs11572048 · VCV3044987

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4791 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4791	ambiguous
REVEL	0.205	benign-leaning
SaProt	LLR -11.49	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.54, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 43 kb · p 4.7e-09 · regional, not allelic
Overall
CADD	25.8	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 1.28% African / African-American · 964/75,032 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.0662% 1,068/1,614,072 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
Remaining individualsnot grpmax-eligible	0.08%	1,250
Admixed American	0.0517%	1,936
Middle Eastern	0.0495%	2,021
South Asian	0.00878%	11,385
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.000932%	107,272

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.Leu720Phe
Coding: c.2160G>C
MANE Select: NM_001253
dbSNP: rs11572048
Type: single nucleotide variant
Location: chr6:44445723 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 41 PDB
Residue 720: the 'interaction with plrg1' region; an α-helix

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

Similar variants

CDC5L p.Ala93= Benign ★★ same type
CDC5L p.Asp236= Benign ★★ same type
CDC5L p.Leu721= Benign ★★ same type
CDC5L p.Ala234Val Uncertain significance ★ ⚠ same type
CDC5L p.Ala457Thr Uncertain significance ★ ⚠ same type
CDC5L p.Ala485Thr Uncertain significance ★ ⚠ same type
CDC5L p.Arg202Lys Uncertain significance ★ ⚠ same type
CDC5L p.Arg202Thr 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/cdc5l-p-leu720phe (accessed [today's date]).

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