Is ACBD5 p.Met70Lys (c.209T>A) pathogenic?

ACBD5 p.Met70Lys (c.209T>A) is classified Uncertain significance in ACBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.8449); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACBD5 p.Met70Lys (c.209T>A)?

ACBD5 p.Met70Lys (c.209T>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD5 p.Met70Lys (c.209T>A) in the general population?

ACBD5 p.Met70Lys (c.209T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACBD5 p.Met70Lys (c.209T>A)?

AlphaMissense predicts likely pathogenic (score 0.8449) — an in-silico prediction, not a clinical call.

ACBD5 p.Met70Lys

c.209T>A · VCV4565556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8449 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8449	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M68K vs ClinVar M70K) — verify the residue.

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: ACBD5
Protein: p.Met70Lys
Coding: c.209T>A
MANE Select: NM_145698
Type: single nucleotide variant
Location: chr10:27235185 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 70: the acb domain; an α-helix

Full ACBD5 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

ACBD5 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
ACBD5 p.Arg384Trp Uncertain significance ★★ ⚠ same condition
ACBD5 p.Arg415Trp Uncertain significance ★★ ⚠ same condition
ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same condition
ACBD5 p.Gln452His Uncertain significance ★★ ⚠ same condition
ACBD5 p.Glu312Lys Uncertain significance ★★ ⚠ same condition
ACBD5 p.Glu493Lys Uncertain significance ★★ ⚠ same condition
ACBD5 p.Gly180Asp 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/acbd5-p-met70lys (accessed [today's date]).

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