Is ACD p.Arg14Pro (c.41G>C) pathogenic?

ACD p.Arg14Pro (c.41G>C) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.859); Absent from gnomAD v4.1.

How common is ACD p.Arg14Pro (c.41G>C) in the general population?

ACD p.Arg14Pro (c.41G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Arg14Pro (c.41G>C)?

AlphaMissense predicts likely pathogenic (score 0.859) — an in-silico prediction, not a clinical call.

ACD p.Arg14Pro

c.41G>C · VCV3765188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.859	likely pathogenic · top 6% in ACD
REVEL	0.308	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	25.7	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.Arg14Pro
Coding: c.41G>C
MANE Select: NM_001082486
Type: single nucleotide variant
Location: chr16:67660180 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 14: an α-helix

Full ACD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACD p.Arg14= Conflicting classifications of pathogenicity ★ same residue
ACD c.645+2T>C Uncertain significance ★★ same type
ACD c.99+5G>A Uncertain significance ★★ same type
ACD c.-20C>T Uncertain significance ★★ same type
ACD c.-24C>T Uncertain significance ★★ same type
ACD c.-26T>G Uncertain significance ★★ same type
ACD c.-29C>A Uncertain significance ★★ same type
ACD c.-29C>T Uncertain significance ★★ same type

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-arg14pro (accessed [today's date]).

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