Is CDYL2 p.Phe342Leu (c.1024T>C) pathogenic?

CDYL2 p.Phe342Leu (c.1024T>C) is classified Uncertain significance in CDYL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely pathogenic (0.9858); Absent from gnomAD v4.1.

How common is CDYL2 p.Phe342Leu (c.1024T>C) in the general population?

CDYL2 p.Phe342Leu (c.1024T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDYL2 p.Phe342Leu (c.1024T>C)?

AlphaMissense predicts likely pathogenic (score 0.9858) — an in-silico prediction, not a clinical call.

CDYL2 p.Phe342Leu

c.1024T>C · VCV3489833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9858 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9858	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -7.23	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 8,100 bp · p 0.00035 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDYL2
Protein: p.Phe342Leu
Coding: c.1024T>C
MANE Select: NM_152342
Type: single nucleotide variant
Location: chr16:80612820 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.08 · 8 PDB

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-phe342leu (accessed [today's date]).

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