Is CDC5L p.Arg202Thr (c.605G>C) pathogenic?

CDC5L p.Arg202Thr (c.605G>C) is classified Uncertain significance in CDC5L (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). AlphaMissense: likely pathogenic (0.7461); Very rare (popmax 8.48e-05%, nfe).

How common is CDC5L p.Arg202Thr (c.605G>C) in the general population?

CDC5L p.Arg202Thr (c.605G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDC5L p.Arg202Thr (c.605G>C)?

AlphaMissense predicts likely pathogenic (score 0.7461) — an in-silico prediction, not a clinical call.

CDC5L p.Arg202Thr

c.605G>C · rs1791245673 · VCV2322212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7461	likely pathogenic
REVEL	0.314	indeterminate
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 43 kb · p 4.7e-09 · regional, not allelic
Overall
CADD	28.2	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 8.48e-05% European (non-Finnish) · 1/1,179,740 alleles

Overall 6.84e-05% 1/1,461,038 alleles · very rare

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.Arg202Thr
Coding: c.605G>C
MANE Select: NM_001253
dbSNP: rs1791245673
Type: single nucleotide variant
Location: chr6:44403874 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 41 PDB
Residue 202: the 'required for interaction with ctnnbl1' region; an α-helix

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

Similar variants

CDC5L p.Arg202Lys Uncertain significance ★ ⚠ same residue
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.Arg321Cys 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-arg202thr (accessed [today's date]).

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