Is ACRBP p.Ser92Cys (c.275C>G) pathogenic?

ACRBP p.Ser92Cys (c.275C>G) is classified Uncertain significance in ACRBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.9132); Ultra-rare (popmax 0.0254%, afr).

How common is ACRBP p.Ser92Cys (c.275C>G) in the general population?

ACRBP p.Ser92Cys (c.275C>G) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about ACRBP p.Ser92Cys (c.275C>G)?

AlphaMissense predicts likely pathogenic (score 0.9132) — an in-silico prediction, not a clinical call.

ACRBP p.Ser92Cys

c.275C>G · rs147903154 · VCV2612601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9132	likely pathogenic
REVEL	0.295	indeterminate
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 7,246 bp · p 0.19 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,908 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00167% 27/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,943
Remaining individualsnot grpmax-eligible	0.0112%	8,926
South Asian	0.0011%	91,084

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.Ser92Cys
Coding: c.275C>G
MANE Select: NM_032489
dbSNP: rs147903154
Type: single nucleotide variant
Location: chr12:6646565 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.09
Residue 92: the 'pro-acr binding' region

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.Arg162Cys Uncertain significance ★ ⚠ same type
ACRBP p.Arg242Gln 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-ser92cys (accessed [today's date]).

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