Is ACD p.Arg245Gly (c.733A>G) pathogenic?

ACD p.Arg245Gly (c.733A>G) is classified Uncertain significance in ACD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-16). AlphaMissense: likely benign (0.0936); Very rare (popmax 0.00204%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Arg245Gly (c.733A>G)?

ACD p.Arg245Gly (c.733A>G) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Arg245Gly (c.733A>G) in the general population?

ACD p.Arg245Gly (c.733A>G) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about ACD p.Arg245Gly (c.733A>G)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

ACD p.Arg245Gly

c.733A>G · rs1466387773 · VCV1768608

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.29	donor loss, 9 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP 0.58, phastCons 0.85
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	19.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00204% European (non-Finnish) · 24/1,178,760 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00171% 25/1,459,740 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,115
African / African-American	0.00133%	74,996

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.Arg245Gly
Coding: c.733A>G
MANE Select: NM_001082486
dbSNP: rs1466387773
Type: single nucleotide variant
Location: chr16:67658729 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 245: the 'interaction with pot1' 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 p.Arg245Lys Uncertain significance ★★ ⚠ same residue
ACD p.Arg245Thr 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-arg245gly (accessed [today's date]).

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