Is ACBD3 p.Met247Val (c.739A>G) pathogenic?

ACBD3 p.Met247Val (c.739A>G) is classified Uncertain significance in ACBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.7288); Very rare (popmax 0.00333%, amr).

How common is ACBD3 p.Met247Val (c.739A>G) in the general population?

ACBD3 p.Met247Val (c.739A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ACBD3 p.Met247Val (c.739A>G)?

AlphaMissense predicts likely pathogenic (score 0.7288) — an in-silico prediction, not a clinical call.

ACBD3 p.Met247Val

c.739A>G · VCV4215058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7288	likely pathogenic
REVEL	0.324	indeterminate
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.00022 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,822 alleles · very rare

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: ACBD3
Protein: p.Met247Val
Coding: c.739A>G
MANE Select: NM_022735
Type: single nucleotide variant
Location: chr1:226159348 (GRCh38)
Gene constraint: LOEUF 0.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50 · 12 PDB
Residue 247: an α-helix; the 'q domain; interaction with pi4kb, tbc1d22a and tbc1d22b' region

Full ACBD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD3 p.Ala177Glu Uncertain significance ★ ⚠ same type
ACBD3 p.Ala177Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala371Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala3Thr Uncertain significance ★ ⚠ same type
ACBD3 p.Ala442Asp Uncertain significance ★ ⚠ same type
ACBD3 p.Ala63Val Uncertain significance ★ ⚠ same type
ACBD3 p.Ala90Gly Uncertain significance ★ ⚠ same type
ACBD3 p.Ala90Thr 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/acbd3-p-met247val (accessed [today's date]).

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