Is CDC5L p.Ala93= (c.279G>A) pathogenic?

CDC5L p.Ala93= (c.279G>A) is classified Benign in CDC5L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). Common (popmax 18%, amr) — too common for a highly-penetrant pathogenic allele.

CDC5L p.Ala93=

Q: How common is CDC5L p.Ala93= (c.279G>A) in the general population?

CDC5L p.Ala93= (c.279G>A) is common (popmax 18%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.279G>A · rs10948136 · VCV1282740

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 18%, amr) — 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 -2.2	GERP -4.6
Overall
CADD	6.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18% Admixed American · 10,802/60,014 alleles

Filtering AF 17.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.6%

Overall 3.62% 58,461/1,613,848 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	18%	6
East Asian	10.1%	10
Finnishnot grpmax-eligible	8.67%	12
South Asian	5.11%	20
Middle Eastern	4.17%	24
Remaining individualsnot grpmax-eligible	3.66%	27
African / African-American	3.2%	31
European (non-Finnish)	2.33%	43
Ashkenazi Jewishnot grpmax-eligible	1.63%	61

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.Ala93=
Coding: c.279G>A
MANE Select: NM_001253
dbSNP: rs10948136
Type: single nucleotide variant
Location: chr6:44392796 (GRCh38)
Gene constraint: LOEUF 0.26 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.94 · 41 PDB
Residue 93: the hth myb-type 2 domain; a DNA-binding region; an α-helix

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

Similar variants

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
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-ala93 (accessed [today's date]).

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