Is ACBD5 p.Thr412Pro (c.1234A>C) pathogenic?

ACBD5 p.Thr412Pro (c.1234A>C) is classified Likely benign in ACBD5 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.0714); Rare (popmax 0.225%, afr).

How common is ACBD5 p.Thr412Pro (c.1234A>C) in the general population?

ACBD5 p.Thr412Pro (c.1234A>C) is rare (popmax 0.225%, afr) (gnomAD).

What do computational predictors say about ACBD5 p.Thr412Pro (c.1234A>C)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

ACBD5 p.Thr412Pro

c.1234A>C · rs147305464 · VCV1113765

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.225%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.80	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 -1.6	GERP -3.6
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	6.951	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 T421P vs ClinVar T412P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.225% African / African-American · 169/75,070 alleles

Filtering AF 0.197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.013% 210/1,614,058 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.225%	444
Remaining individualsnot grpmax-eligible	0.0368%	2,717
Admixed American	0.0233%	4,288
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,338

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACBD5
Protein: p.Thr412Pro
Coding: c.1234A>C
MANE Select: NM_145698
dbSNP: rs147305464
Type: single nucleotide variant
Location: chr10:27208416 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 412: the 'disordered' region

Full ACBD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD5 p.Arg433Ter Pathogenic/Likely pathogenic ★★ same type
ACBD5 p.Ala182Thr Uncertain significance ★★ ⚠ same type
ACBD5 p.Arg384Trp Uncertain significance ★★ ⚠ same type
ACBD5 p.Arg415Trp Uncertain significance ★★ ⚠ same type
ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same type
ACBD5 p.Gln452His Uncertain significance ★★ ⚠ same type
ACBD5 p.Glu312Lys Uncertain significance ★★ ⚠ same type
ACBD5 p.Glu493Lys 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/acbd5-p-thr412pro (accessed [today's date]).

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