Is ACRBP p.Arg162Cys (c.484C>T) pathogenic?

ACRBP p.Arg162Cys (c.484C>T) is classified Uncertain significance in ACRBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.1402); Very rare (popmax 0.00267%, afr).

How common is ACRBP p.Arg162Cys (c.484C>T) in the general population?

ACRBP p.Arg162Cys (c.484C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ACRBP p.Arg162Cys (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1402) — an in-silico prediction, not a clinical call.

ACRBP p.Arg162Cys

c.484C>T · VCV3481984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1402	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -9.82	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 5.1	GERP 0.45, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 7,246 bp · p 0.19 · regional, not allelic
Overall
CADD	23.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,776 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,611,658 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,388
East Asian	0.00223%	44,890
South Asian	0.0022%	45,420
European (non-Finnish)	0.00017%	589,463

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: ACRBP
Protein: p.Arg162Cys
Coding: c.484C>T
MANE Select: NM_032489
Type: single nucleotide variant
Location: chr12:6644597 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.09

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

Similar variants

ACRBP p.Ala192Val Uncertain significance ★ ⚠ same type
ACRBP p.Ala244Thr Uncertain significance ★ ⚠ same type
ACRBP p.Ala24Thr Uncertain significance ★ ⚠ same type
ACRBP p.Ala324Gly Uncertain significance ★ ⚠ same type
ACRBP p.Ala345Val Uncertain significance ★ ⚠ same type
ACRBP p.Arg110Cys Uncertain significance ★ ⚠ same type
ACRBP p.Arg242Gln Uncertain significance ★ ⚠ same type
ACRBP p.Arg273Gln 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/acrbp-p-arg162cys (accessed [today's date]).

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