Is CDC5L p.Asp236= (c.708C>T) pathogenic?

CDC5L p.Asp236= (c.708C>T) is classified Benign in CDC5L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). Common (popmax 58%, eas) — too common for a highly-penetrant pathogenic allele.

CDC5L p.Asp236=

Q: How common is CDC5L p.Asp236= (c.708C>T) in the general population?

CDC5L p.Asp236= (c.708C>T) is common (popmax 58%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.708C>T · rs6934058 · VCV1228167

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 58%, eas) — too common for a highly-penetrant pathogenic allele

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 0.67	GERP -2.5, phastCons 1
Overall
CADD	8.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 58% East Asian · 26,008/44,824 alleles

Filtering AF 57.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.2%

Overall 12.2% 196,451/1,612,186 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	58%	2
South Asian	30.9%	3
African / African-American	21.1%	5
Remaining individualsnot grpmax-eligible	14.7%	7
Admixed American	12.3%	8
Finnishnot grpmax-eligible	12.1%	8
Ashkenazi Jewishnot grpmax-eligible	10.9%	9
Middle Eastern	10.3%	10
European (non-Finnish)	8.35%	12
Amishnot grpmax-eligible	6.8%	15

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.Asp236=
Coding: c.708C>T
MANE Select: NM_001253
dbSNP: rs6934058
Type: single nucleotide variant
Location: chr6:44403977 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 41 PDB

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

Similar variants

CDC5L p.Ala93= 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
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-asp236 (accessed [today's date]).

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