Is ACD p.Glu231Gln (c.691G>C) pathogenic?

ACD p.Glu231Gln (c.691G>C) is classified Uncertain significance in ACD (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-26). AlphaMissense: likely benign (0.1251); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACD p.Glu231Gln (c.691G>C)?

ACD p.Glu231Gln (c.691G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Glu231Gln (c.691G>C) in the general population?

ACD p.Glu231Gln (c.691G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Glu231Gln (c.691G>C)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

ACD p.Glu231Gln

c.691G>C · VCV3479937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Glu231Gln
Coding: c.691G>C
MANE Select: NM_001082486
Type: single nucleotide variant
Location: chr16:67658771 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 231: the 'interaction with pot1' region; an α-helix

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.Glu231= Likely benign ★★ 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-glu231gln (accessed [today's date]).

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