Is ACD p.Arg393fs (c.1177del) pathogenic?

ACD p.Arg393fs (c.1177del) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-20). Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Arg393fs (c.1177del)?

ACD p.Arg393fs (c.1177del) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

ACD p.Arg393fs

c.1177del · VCV3657153

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 10 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.47	GERP -2.8

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

Variant & gene context

Gene: ACD
Protein: p.Arg393fs
Coding: c.1177del
MANE Select: NM_001082486
Type: Deletion
Location: chr16:67658015 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 393: the 'disordered' region

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.Arg393Lys Uncertain significance ★★ ⚠ same residue
ACD p.Pro203fs Uncertain significance ★★ same condition
ACD p.Pro273_Ser276del Uncertain significance ★★ same condition
ACD p.Pro455fs Uncertain significance ★★ same condition
ACD p.Arg6fs Likely pathogenic ★ same condition
ACD p.Lys84del Pathogenic ★ same condition
ACD p.Thr51fs Likely pathogenic ★ same condition
ACD c.742+4del 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-arg393fs (accessed [today's date]).

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