Is ACD p.Glu115Lys (c.343G>A) pathogenic?

ACD p.Glu115Lys (c.343G>A) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-27). AlphaMissense: ambiguous (0.5182); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACD p.Glu115Lys (c.343G>A)?

ACD p.Glu115Lys (c.343G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Glu115Lys (c.343G>A) in the general population?

ACD p.Glu115Lys (c.343G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Glu115Lys (c.343G>A)?

AlphaMissense predicts ambiguous (score 0.5182) — an in-silico prediction, not a clinical call.

ACD p.Glu115Lys

c.343G>A · rs141113896 · VCV2452434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5182 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5182	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -9.95	tolerated
Splicing
SpliceAI	Δ0.40	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	34.0	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.Glu115Lys
Coding: c.343G>A
MANE Select: NM_001082486
dbSNP: rs141113896
Type: single nucleotide variant
Location: chr16:67659607 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 115: 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.Glu115Gln Uncertain significance ★ ⚠ same residue
ACD p.Glu115Ter 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

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-glu115lys (accessed [today's date]).

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