Is ACD p.Arg27Gln (c.80G>A) pathogenic?

ACD p.Arg27Gln (c.80G>A) is classified Benign/Likely benign in ACD (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0883); Low-frequency (popmax 1.05%, sas); Associated with dyskeratosis congenita, autosomal dominant 6.

What condition is associated with ACD p.Arg27Gln (c.80G>A)?

ACD p.Arg27Gln (c.80G>A) is associated with dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Arg27Gln (c.80G>A) in the general population?

ACD p.Arg27Gln (c.80G>A) is low-frequency (popmax 1.05%, sas) (gnomAD).

What do computational predictors say about ACD p.Arg27Gln (c.80G>A)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

ACD p.Arg27Gln

c.80G>A · rs142507451 · VCV475768

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, autosomal dominant 6

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP -2.8, phastCons 0.008
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	13.79	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.05% South Asian · 958/91,086 alleles

Filtering AF 0.996% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.974%

Overall 0.268% 4,329/1,612,532 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.05%	95
European (non-Finnish)	0.263%	381
Middle Eastern	0.247%	404
Remaining individualsnot grpmax-eligible	0.219%	456
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0906%	1,104
Admixed American	0.055%	1,819
Finnishnot grpmax-eligible	0.024%	4,171
East Asian	0.00669%	14,951
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598

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.Arg27Gln
Coding: c.80G>A
MANE Select: NM_001082486
dbSNP: rs142507451
Type: single nucleotide variant
Location: chr16:67660141 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 27: a β-strand

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.Arg27= Likely benign ★ same residue
ACD p.Gly27Arg Uncertain significance ★ same residue
ACD p.Gly27= 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
ACD c.-26T>G 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-arg27gln (accessed [today's date]).

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