Is ACBD5 p.Ser435Cys (c.1303A>T) pathogenic?

ACBD5 p.Ser435Cys (c.1303A>T) is classified Uncertain significance in ACBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.1388); Ultra-rare (popmax 0.02%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACBD5 p.Ser435Cys (c.1303A>T)?

ACBD5 p.Ser435Cys (c.1303A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACBD5 p.Ser435Cys (c.1303A>T) in the general population?

ACBD5 p.Ser435Cys (c.1303A>T) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about ACBD5 p.Ser435Cys (c.1303A>T)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

ACBD5 p.Ser435Cys

c.1303A>T · VCV3997592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -8.64	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 2.3	GERP 0.67, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	23.6	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 S444C vs ClinVar S435C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 9/44,894 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000558% 9/1,614,102 alleles · ultra-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: ACBD5
Protein: p.Ser435Cys
Coding: c.1303A>T
MANE Select: NM_145698
Type: single nucleotide variant
Location: chr10:27208347 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 435: the 'disordered' region

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-ser435cys (accessed [today's date]).

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