Is CDYL2 p.Gly162Ser (c.484G>A) pathogenic?

CDYL2 p.Gly162Ser (c.484G>A) is classified Uncertain significance in CDYL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.0648); Very rare (popmax 0.00329%, sas).

How common is CDYL2 p.Gly162Ser (c.484G>A) in the general population?

CDYL2 p.Gly162Ser (c.484G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CDYL2 p.Gly162Ser (c.484G>A)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

CDYL2 p.Gly162Ser

c.484G>A · VCV3831098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.24	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 -2.4	GERP -3.1
Regional constraint	o/e 1.12	unconstrained · MANE · 183 kb · p 0.014 · regional, not allelic
Overall
CADD	0.421	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0018% 29/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
African / African-American	0.00267%	37,460
European (non-Finnish)	0.00186%	53,638
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Gly162Ser
Coding: c.484G>A
MANE Select: NM_152342
Type: single nucleotide variant
Location: chr16:80684670 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.08 · 8 PDB
Residue 162: 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-gly162ser (accessed [today's date]).

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