Is ACD p.Arg94Leu (c.281G>T) pathogenic?

ACD p.Arg94Leu (c.281G>T) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). AlphaMissense: ambiguous (0.5617); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACD p.Arg94Leu (c.281G>T)?

ACD p.Arg94Leu (c.281G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Arg94Leu (c.281G>T) in the general population?

ACD p.Arg94Leu (c.281G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Arg94Leu (c.281G>T)?

AlphaMissense predicts ambiguous (score 0.5617) — an in-silico prediction, not a clinical call.

ACD p.Arg94Leu

c.281G>T · VCV3261527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5617 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5617	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -9.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.56, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACD
Protein: p.Arg94Leu
Coding: c.281G>T
MANE Select: NM_001082486
Type: single nucleotide variant
Location: chr16:67659757 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 94: a β-strand

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

Similar variants

ACD p.Arg94Gln Uncertain significance ★ ⚠ same residue
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A Uncertain significance ★★ same condition
ACD c.-30C>T Uncertain significance ★★ same condition
ACD c.-35C>T Uncertain significance ★★ same condition
ACD c.-36C>G Uncertain significance ★★ same condition
ACD c.-9G>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-arg94leu (accessed [today's date]).

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