Is ACBD7 p.Ala74Pro (c.220G>C) pathogenic?

ACBD7 p.Ala74Pro (c.220G>C) is classified Uncertain significance in ACBD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely pathogenic (0.8125); Absent from gnomAD v4.1.

How common is ACBD7 p.Ala74Pro (c.220G>C) in the general population?

ACBD7 p.Ala74Pro (c.220G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACBD7 p.Ala74Pro (c.220G>C)?

AlphaMissense predicts likely pathogenic (score 0.8125) — an in-silico prediction, not a clinical call.

ACBD7 p.Ala74Pro

c.220G>C · VCV3261397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8125 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8125	likely pathogenic · top 3% in ACBD7
REVEL	0.326	indeterminate
SaProt	LLR -12.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 5.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 10 kb · p 0.43 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ACBD7
Protein: p.Ala74Pro
Coding: c.220G>C
MANE Select: NM_001039844
Type: single nucleotide variant
Location: chr10:15078577 (GRCh38)
Gene constraint: LOEUF 1.515 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.95 · 1 PDB
Residue 74: the acb domain; an α-helix

Full ACBD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD7 p.Ala2Asp Uncertain significance ★ ⚠ same type
ACBD7 p.Ala71Val Uncertain significance ★ ⚠ same type
ACBD7 p.Arg9Ser Uncertain significance ★ ⚠ same type
ACBD7 p.Glu28Gly Uncertain significance ★ ⚠ same type
ACBD7 p.Gly39Val Uncertain significance ★ ⚠ same type
ACBD7 p.Gly65Glu Uncertain significance ★ ⚠ same type
ACBD7 p.Gly87Arg Uncertain significance ★ ⚠ same type
ACBD7 p.Ile88Thr 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/acbd7-p-ala74pro (accessed [today's date]).

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