Is CDYL p.Asp263Gly (c.788A>G) pathogenic?

CDYL p.Asp263Gly (c.788A>G) is classified Uncertain significance in CDYL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: ambiguous (0.4959); Very rare (popmax 0.0022%, nfe).

How common is CDYL p.Asp263Gly (c.788A>G) in the general population?

CDYL p.Asp263Gly (c.788A>G) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about CDYL p.Asp263Gly (c.788A>G)?

AlphaMissense predicts ambiguous (score 0.4959) — an in-silico prediction, not a clinical call.

CDYL p.Asp263Gly

c.788A>G · VCV3831093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4959	ambiguous
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 159 kb · p 0.037 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D317G vs ClinVar D263G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,180,042 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00173% 28/1,614,120 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,942

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.Asp263Gly
Coding: c.788A>G
MANE Select: NM_004824
Type: single nucleotide variant
Location: chr6:4935611 (GRCh38)
Gene constraint: LOEUF 0.293 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 263: 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-asp263gly (accessed [today's date]).

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