Is ACD p.Ala112= (c.336G>A) pathogenic?

ACD p.Ala112= (c.336G>A) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). Absent from gnomAD v4.1.

How common is ACD p.Ala112= (c.336G>A) in the general population?

ACD p.Ala112= (c.336G>A) is absent from gnomAD v4.1 (gnomAD).

ACD p.Ala112=

c.336G>A · VCV3342653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	donor gain · deltas
Pangolin	Δ0.64	gain · loss 0.53 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 0.54, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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.Ala112=
Coding: c.336G>A
MANE Select: NM_001082486
Type: single nucleotide variant
Location: chr16:67659702 (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

Similar variants

ACD p.Ala112Thr Uncertain significance ★ ⚠ 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-ala112 (accessed [today's date]).

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