Is ACBD5 p.Arg425Cys (c.1273C>T) pathogenic?

ACBD5 p.Arg425Cys (c.1273C>T) is classified Uncertain significance in ACBD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). AlphaMissense: likely benign (0.3365); Very rare (popmax 0.005%, amr).

How common is ACBD5 p.Arg425Cys (c.1273C>T) in the general population?

ACBD5 p.Arg425Cys (c.1273C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ACBD5 p.Arg425Cys (c.1273C>T)?

AlphaMissense predicts likely benign (score 0.3365) — an in-silico prediction, not a clinical call.

ACBD5 p.Arg425Cys

c.1273C>T · rs779982287 · VCV960903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3365	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic
Overall
CADD	33.0	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 R434C vs ClinVar R425C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,986 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.0013% 21/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,448
East Asian	0.00223%	44,892
South Asian	0.0022%	45,544
European (non-Finnish)	0.000932%	107,273

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.Arg425Cys
Coding: c.1273C>T
MANE Select: NM_145698
dbSNP: rs779982287
Type: single nucleotide variant
Location: chr10:27208377 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.49 · 1 PDB
Residue 425: the 'disordered' region

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

Similar variants

ACBD5 p.Arg425Gly Uncertain significance ★ ⚠ same residue
ACBD5 p.Arg425His Uncertain significance ★ ⚠ same residue
ACBD5 p.Arg425Leu Uncertain significance ★ ⚠ same residue
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

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-arg425cys (accessed [today's date]).

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