Is CDADC1 p.Tyr229Phe (c.686A>T) pathogenic?

CDADC1 p.Tyr229Phe (c.686A>T) is classified Uncertain significance in CDADC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.0772); Very rare (popmax 6.86e-05%).

How common is CDADC1 p.Tyr229Phe (c.686A>T) in the general population?

CDADC1 p.Tyr229Phe (c.686A>T) is very rare (popmax 6.86e-05%) (gnomAD).

What do computational predictors say about CDADC1 p.Tyr229Phe (c.686A>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CDADC1 p.Tyr229Phe

c.686A>T · VCV3829678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.52	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 4	GERP 0.97, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 44 kb · p 5.1e-05 · regional, not allelic
Overall
CADD	16.61	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 6.86e-05%

Overall 6.86e-05% 1/1,458,266 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: CDADC1
Protein: p.Tyr229Phe
Coding: c.686A>T
MANE Select: NM_030911
Type: single nucleotide variant
Location: chr13:49267745 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.53 · 4 PDB
Residue 229: an α-helix

Full CDADC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDADC1 p.Gly119Glu Uncertain significance ★★ ⚠ same type
CDADC1 p.Ala110Thr Uncertain significance ★ ⚠ same type
CDADC1 p.Arg17Pro Uncertain significance ★ ⚠ same type
CDADC1 p.Arg273Ser Uncertain significance ★ ⚠ same type
CDADC1 p.Arg300His Uncertain significance ★ ⚠ same type
CDADC1 p.Arg332Gln Uncertain significance ★ ⚠ same type
CDADC1 p.Arg510His Uncertain significance ★ ⚠ same type
CDADC1 p.Asn247Ser 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/cdadc1-p-tyr229phe (accessed [today's date]).

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