Is CDYL p.Gln528His (c.1584G>C) pathogenic?

CDYL p.Gln528His (c.1584G>C) is classified Uncertain significance in CDYL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely pathogenic (0.6439); Very rare (popmax 0.000254%, nfe).

How common is CDYL p.Gln528His (c.1584G>C) in the general population?

CDYL p.Gln528His (c.1584G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CDYL p.Gln528His (c.1584G>C)?

AlphaMissense predicts likely pathogenic (score 0.6439) — an in-silico prediction, not a clinical call.

CDYL p.Gln528His

c.1584G>C · rs1561729465 · VCV2290976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6439	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -6.82	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 0.23	GERP -4.2, phastCons 0.75
Regional constraint	o/e 0.77	unconstrained · MANE · 1,662 bp · p 0.045 · regional, not allelic
Overall
CADD	18.79	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 Q582H vs ClinVar Q528H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,020 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,838 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: CDYL
Protein: p.Gln528His
Coding: c.1584G>C
MANE Select: NM_004824
dbSNP: rs1561729465
Type: single nucleotide variant
Location: chr6:4954005 (GRCh38)
Gene constraint: LOEUF 0.293 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 528: an α-helix; the 'acetyl-coa-binding domain' 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-gln528his (accessed [today's date]).

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