Is ACD p.Arg211Ter (c.631C>T) pathogenic?

ACD p.Arg211Ter (c.631C>T) is classified Uncertain significance in ACD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0134%, eas); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Arg211Ter (c.631C>T)?

ACD p.Arg211Ter (c.631C>T) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Arg211Ter (c.631C>T) in the general population?

ACD p.Arg211Ter (c.631C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ACD p.Arg211Ter

c.631C>T · rs1339068886 · VCV1440000

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 7 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.8	GERP -2.6, phastCons 0.008
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

Grpmax group 0.0134% East Asian · 6/44,892 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00161% 26/1,613,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
European (non-Finnish)	0.0017%	58,996

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.Arg211Ter
Coding: c.631C>T
MANE Select: NM_001082486
dbSNP: rs1339068886
Type: single nucleotide variant
Location: chr16:67658942 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 211: 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.Arg211Gln 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
ACD c.-29C>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-arg211ter (accessed [today's date]).

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