Is ACD p.Cys344= (c.1032C>T) pathogenic?

ACD p.Cys344= (c.1032C>T) is classified Likely benign in ACD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0302%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Cys344= (c.1032C>T)?

ACD p.Cys344= (c.1032C>T) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Cys344= (c.1032C>T) in the general population?

ACD p.Cys344= (c.1032C>T) is ultra-rare (popmax 0.0302%, amr) (gnomAD).

ACD p.Cys344=

c.1032C>T · rs776364958 · VCV1104392

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0302%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.4	GERP -2.5
Overall
CADD	0.481	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0302% Admixed American · 18/59,518 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.00118% 19/1,607,170 alleles · ultra-rare exomes 18/1,454,940 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0302%	3,307
European (non-Finnish)	8.5e-05%	1,176,046

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.Cys344=
Coding: c.1032C>T
MANE Select: NM_001082486
dbSNP: rs776364958
Type: single nucleotide variant
Location: chr16:67658160 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 344: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita, autosomal dominant 6

Similar variants

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
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A Uncertain significance ★★ same condition
ACD c.-29C>T Uncertain significance ★★ same condition
ACD c.-30C>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-cys344 (accessed [today's date]).

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