Is ACD p.Cys151Ter (c.453C>A) pathogenic?

ACD p.Cys151Ter (c.453C>A) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Cys151Ter (c.453C>A)?

ACD p.Cys151Ter (c.453C>A) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Cys151Ter (c.453C>A) in the general population?

ACD p.Cys151Ter (c.453C>A) is absent from gnomAD v4.1 (gnomAD).

ACD p.Cys151Ter

c.453C>A · rs2543606725 · VCV2027967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.7	GERP -0.62, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACD
Protein: p.Cys151Ter
Coding: c.453C>A
MANE Select: NM_001082486
dbSNP: rs2543606725
Type: single nucleotide variant
Location: chr16:67659380 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 151: 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.Cys151Phe Uncertain significance ★★ ⚠ same residue
ACD p.Cys151Ser Uncertain significance ★ ⚠ same residue
ACD p.Cys151Tyr Uncertain significance ★ ⚠ same residue
ACD p.Cys151= Likely benign ★ same residue
ACD c.645+2T>C Uncertain significance ★★ same condition
ACD c.99+5G>A Uncertain significance ★★ same condition
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-24C>T 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-cys151ter (accessed [today's date]).

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