Is CDYL p.Glu170Lys (c.508G>A) pathogenic?

CDYL p.Glu170Lys (c.508G>A) is classified Uncertain significance in CDYL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: likely benign (0.0959); Rare (popmax 0.143%, eas).

How common is CDYL p.Glu170Lys (c.508G>A) in the general population?

CDYL p.Glu170Lys (c.508G>A) is rare (popmax 0.143%, eas) (gnomAD).

What do computational predictors say about CDYL p.Glu170Lys (c.508G>A)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

CDYL p.Glu170Lys

c.508G>A · rs147719814 · VCV3141778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.143%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 159 kb · p 0.037 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E224K vs ClinVar E170K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% East Asian · 64/44,894 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0379% 611/1,614,098 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.143%	701
European (non-Finnish)	0.0437%	2,287
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Middle Eastern	0.0164%	6,084
African / African-American	0.0133%	7,494
Admixed American	0.00833%	12,002
Finnishnot grpmax-eligible	0.00156%	64,034
South Asian	0.0011%	91,078

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: CDYL
Protein: p.Glu170Lys
Coding: c.508G>A
MANE Select: NM_004824
dbSNP: rs147719814
Type: single nucleotide variant
Location: chr6:4892196 (GRCh38)
Gene constraint: LOEUF 0.293 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 170: a modified residue (phosphoserine); the 'interaction with ezh2' region

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

Similar variants

CDYL p.Ala136Val Uncertain significance ★ ⚠ same type
CDYL p.Ala154Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala182Ser Uncertain significance ★ ⚠ same type
CDYL p.Ala183Val Uncertain significance ★ ⚠ same type
CDYL p.Ala195Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala329Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala527Ser Uncertain significance ★ ⚠ same type
CDYL p.Arg11Lys 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/cdyl-p-glu170lys (accessed [today's date]).

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