Is ACD p.Ser334= (c.1002C>T) pathogenic?

ACD p.Ser334= (c.1002C>T) is classified Likely benign in ACD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-18). Very rare (popmax 0.00492%, nfe); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Ser334= (c.1002C>T)?

ACD p.Ser334= (c.1002C>T) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Ser334= (c.1002C>T) in the general population?

ACD p.Ser334= (c.1002C>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

ACD p.Ser334=

c.1002C>T · rs372195324 · VCV434066

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.054	GERP -2
Overall
CADD	1.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 58/1,179,224 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00378% 61/1,612,112 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,331
Remaining individualsnot grpmax-eligible	0.00481%	20,807

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.Ser334=
Coding: c.1002C>T
MANE Select: NM_001082486
dbSNP: rs372195324
Type: single nucleotide variant
Location: chr16:67658190 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 334: 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.Ser334Arg Uncertain significance ★ ⚠ same residue
ACD p.Ser334Thr Uncertain significance ★ ⚠ 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
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A 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-ser334 (accessed [today's date]).

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