Is ACD p.Pro273= (c.819C>T) pathogenic?

ACD p.Pro273= (c.819C>T) is classified Benign/Likely benign in ACD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.648%, afr); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Pro273= (c.819C>T)?

ACD p.Pro273= (c.819C>T) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Pro273= (c.819C>T) in the general population?

ACD p.Pro273= (c.819C>T) is rare (popmax 0.648%, afr) (gnomAD).

ACD p.Pro273=

c.819C>T · rs138740815 · VCV542418

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.648%, afr)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.11	GERP -2.8
Overall
CADD	6.873	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.648% African / African-American · 479/73,952 alleles

Filtering AF 0.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0616% 965/1,566,650 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.648%	154
Admixed American	0.27%	371
Middle Eastern	0.121%	829
Remaining individualsnot grpmax-eligible	0.0928%	1,078
European (non-Finnish)	0.0236%	4,229

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.Pro273=
Coding: c.819C>T
MANE Select: NM_001082486
dbSNP: rs138740815
Type: single nucleotide variant
Location: chr16:67658565 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 273: 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.Pro273_Ser276del 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-pro273 (accessed [today's date]).

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