Is ACD p.Ala184fs (c.545dup) pathogenic?

ACD p.Ala184fs (c.545dup) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-20). Very rare (popmax 0.005%, amr); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Ala184fs (c.545dup)?

ACD p.Ala184fs (c.545dup) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Ala184fs (c.545dup) in the general population?

ACD p.Ala184fs (c.545dup) is very rare (popmax 0.005%, amr) (gnomAD).

ACD p.Ala184fs

c.545dup · rs1567641214 · VCV1426430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.87	GERP -0.59

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,024 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000342% 5/1,461,632 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,008
European (non-Finnish)	0.000169%	590,009

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: ACD
Protein: p.Ala184fs
Coding: c.545dup
MANE Select: NM_001082486
dbSNP: rs1567641214
Type: Duplication
Location: chr16:67659027 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 184: the 'interaction with pot1' region; an α-helix

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.Ala184Val Uncertain significance ★ ⚠ same residue
ACD p.Asp121fs Uncertain significance ★★ same condition
ACD c.493+6dup Uncertain significance ★ same condition
ACD p.Ala184Ser Uncertain significance ★ ⚠ same residue
ACD p.Ala184Thr Uncertain significance ★ ⚠ same residue
ACD p.Gly102_Val103insCysGly Uncertain significance ★ same condition
ACD p.Phe375_Val376insLysGluPhe Uncertain significance ★ same condition
ACD p.Pro45fs 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-ala184fs (accessed [today's date]).

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