Is ACBD5 p.Ser471Ala (c.1411T>G) pathogenic?

ACBD5 p.Ser471Ala (c.1411T>G) is classified Uncertain significance in ACBD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-01). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with ACBD5 p.Ser471Ala (c.1411T>G)?

ACBD5 p.Ser471Ala (c.1411T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD5 p.Ser471Ala (c.1411T>G) in the general population?

ACBD5 p.Ser471Ala (c.1411T>G) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about ACBD5 p.Ser471Ala (c.1411T>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

ACBD5 p.Ser471Ala

c.1411T>G · rs750618594 · VCV1466927

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.04	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 6.4	GERP 1.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	17.42	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 S480A vs ClinVar S471A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,072 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00167% 27/1,613,136 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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.Ser471Ala
Coding: c.1411T>G
MANE Select: NM_145698
dbSNP: rs750618594
Type: single nucleotide variant
Location: chr10:27205242 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB

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.Ser471= Likely benign ★ same residue
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

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-ser471ala (accessed [today's date]).

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