Is CDYL2 p.Val404Phe (c.1210G>T) pathogenic?

CDYL2 p.Val404Phe (c.1210G>T) is classified Uncertain significance in CDYL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely pathogenic (0.683); Very rare (popmax 0.00222%, sas).

How common is CDYL2 p.Val404Phe (c.1210G>T) in the general population?

CDYL2 p.Val404Phe (c.1210G>T) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about CDYL2 p.Val404Phe (c.1210G>T)?

AlphaMissense predicts likely pathogenic (score 0.683) — an in-silico prediction, not a clinical call.

CDYL2 p.Val404Phe

c.1210G>T · rs368472250 · VCV2238531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.683	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -5.41	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 3.9	GERP 0.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 8,289 bp · p 0.85 · regional, not allelic
Overall
CADD	24.8	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 0.00222% South Asian · 2/90,266 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000138% 2/1,454,536 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: CDYL2
Protein: p.Val404Phe
Coding: c.1210G>T
MANE Select: NM_152342
dbSNP: rs368472250
Type: single nucleotide variant
Location: chr16:80612634 (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.Val404Ile Uncertain significance ★ ⚠ same residue
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

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-val404phe (accessed [today's date]).

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