Is ACD p.Glu21fs (c.63_64del) pathogenic?

ACD p.Glu21fs (c.6364del) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Glu21fs (c.63_64del)?

ACD p.Glu21fs (c.63_64del) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

ACD p.Glu21fs

c.63_64del · VCV4804987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -0.85, phastCons 0.025

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ACD
Protein: p.Glu21fs
Coding: c.63_64del
MANE Select: NM_001082486
Type: Microsatellite
Location: chr16:67660157 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 21: a β-strand

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

Disease context

dyskeratosis congenita, autosomal dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACD p.Glu21= Likely benign ★★ same residue
ACD p.Glu83del Pathogenic ★ same condition
ACD c.830-11CTC[2] Uncertain significance ★ same condition
ACD p.Pro270del Uncertain significance ★ same condition
ACD c.337-5_337-3del Likely benign ★ same condition
ACD p.Pro21= Likely benign ★ same residue
ACD c.645+2T>C Uncertain significance ★★ same condition
ACD c.71_72delGGinsCC Uncertain significance ★★ same condition

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/acd-p-glu21fs (accessed [today's date]).

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