Is CDYL2 p.Ser142Arg (c.424A>C) pathogenic?

CDYL2 p.Ser142Arg (c.424A>C) is classified Uncertain significance in CDYL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.8722); Very rare (popmax 0.00212%, nfe).

How common is CDYL2 p.Ser142Arg (c.424A>C) in the general population?

CDYL2 p.Ser142Arg (c.424A>C) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about CDYL2 p.Ser142Arg (c.424A>C)?

AlphaMissense predicts likely pathogenic (score 0.8722) — an in-silico prediction, not a clinical call.

CDYL2 p.Ser142Arg

c.424A>C · VCV3831100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8722	likely pathogenic
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 183 kb · p 0.014 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,016 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,201
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: CDYL2
Protein: p.Ser142Arg
Coding: c.424A>C
MANE Select: NM_152342
Type: single nucleotide variant
Location: chr16:80684730 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.08 · 8 PDB
Residue 142: the 'disordered' region

Full CDYL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDYL2 p.Gly355= Benign ★★ same type
CDYL2 p.Thr261= Benign ★★ same type
CDYL2 p.Ala114Gly Uncertain significance ★ ⚠ same type
CDYL2 p.Ala114Thr Uncertain significance ★ ⚠ same type
CDYL2 p.Ala286Val Uncertain significance ★ ⚠ same type
CDYL2 p.Ala334Thr Uncertain significance ★ ⚠ same type
CDYL2 p.Ala341Gly Uncertain significance ★ ⚠ same type
CDYL2 p.Ala362Thr 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/cdyl2-p-ser142arg (accessed [today's date]).

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