Is ACD p.Arg383Gln (c.1148G>A) pathogenic?

ACD p.Arg383Gln (c.1148G>A) is classified Conflicting classifications of pathogenicity in ACD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0691); Ultra-rare (popmax 0.018%, amr); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Arg383Gln (c.1148G>A)?

ACD p.Arg383Gln (c.1148G>A) is associated with Inborn genetic diseases, dyskeratosis congenita, autosomal dominant 6 (ClinVar).

How common is ACD p.Arg383Gln (c.1148G>A) in the general population?

ACD p.Arg383Gln (c.1148G>A) is ultra-rare (popmax 0.018%, amr) (gnomAD).

What do computational predictors say about ACD p.Arg383Gln (c.1148G>A)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

ACD p.Arg383Gln

c.1148G>A · rs200293827 · VCV838233

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.5	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	0.584	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 0.018% Admixed American · 9/50,042 alleles

Filtering AF 0.0159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0147% 227/1,547,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.018%	5,560
European (non-Finnish)	0.0179%	5,576
Remaining individualsnot grpmax-eligible	0.0118%	8,495
East Asian	0.0045%	22,227
African / African-American	0.00275%	36,381
Finnishnot grpmax-eligible	0.00164%	61,156

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.Arg383Gln
Coding: c.1148G>A
MANE Select: NM_001082486
dbSNP: rs200293827
Type: single nucleotide variant
Location: chr16:67658044 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB

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.Arg383Gly Uncertain significance ★ ⚠ same residue
ACD p.Arg383Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg383gln (accessed [today's date]).

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