Is ACBD4 p.Pro210Leu (c.629C>T) pathogenic?

ACBD4 p.Pro210Leu (c.629C>T) is classified Uncertain significance in ACBD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.0011%, sas).

How common is ACBD4 p.Pro210Leu (c.629C>T) in the general population?

ACBD4 p.Pro210Leu (c.629C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ACBD4 p.Pro210Leu (c.629C>T)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

ACBD4 p.Pro210Leu

c.629C>T · rs1372354843 · VCV2204443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.51	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 0.75	GERP -0.48, phastCons 0.004
Regional constraint	o/e 1.02	unconstrained · MANE · 6,861 bp · p 0.72 · regional, not allelic
Overall
CADD	10.04	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P207S vs ClinVar P210L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,030 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,754 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,030
European (non-Finnish)	0.000593%	168,566

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: ACBD4
Protein: p.Pro210Leu
Coding: c.629C>T
MANE Select: NM_001135705
dbSNP: rs1372354843
Type: single nucleotide variant
Location: chr17:45137968 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 1 PDB

Full ACBD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACBD4 c.*20T>A Uncertain significance ★ same type
ACBD4 c.*27A>G Uncertain significance ★ same type
ACBD4 c.*38T>C Uncertain significance ★ same type
ACBD4 c.*3G>A Uncertain significance ★ same type
ACBD4 c.*51T>G Uncertain significance ★ same type
ACBD4 c.*54G>A Uncertain significance ★ same type
ACBD4 p.Ala282= Uncertain significance ★ same type
ACBD4 p.Ala282Glu 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/acbd4-p-pro210leu (accessed [today's date]).

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