Is ACSBG2 p.Pro601Arg (c.1802C>G) pathogenic?

ACSBG2 p.Pro601Arg (c.1802C>G) is classified Benign in ACSBG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-26). AlphaMissense: likely benign (0.0968); Common (popmax 6.15%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ACSBG2 p.Pro601Arg (c.1802C>G)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

ACSBG2 p.Pro601Arg

Q: How common is ACSBG2 p.Pro601Arg (c.1802C>G) in the general population?

ACSBG2 p.Pro601Arg (c.1802C>G) is common (popmax 6.15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1802C>G · rs35609668 · VCV773082

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.15%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.05	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 -0.31	GERP -1
Regional constraint	o/e 0.89	unconstrained · MANE · 49 kb · p 0.0022 · regional, not allelic
Overall
CADD	7.294	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 6.15% African / African-American · 4,614/74,994 alleles

Filtering AF 6% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.94%

Overall 0.334% 5,391/1,614,086 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.15%	16
Middle Eastern	0.511%	196
Admixed American	0.493%	203
Remaining individualsnot grpmax-eligible	0.486%	206
South Asian	0.0253%	3,960
European (non-Finnish)	0.0104%	9,594

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: ACSBG2
Protein: p.Pro601Arg
Coding: c.1802C>G
MANE Select: NM_030924
dbSNP: rs35609668
Type: single nucleotide variant
Location: chr19:6187720 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.67
Residue 601: a UniProt-annotated variant site (in)

Full ACSBG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSBG2 c.907-6A>C Benign ★★ same type
ACSBG2 p.Ala399= Benign ★★ same type
ACSBG2 p.Ala180Val Uncertain significance ★ ⚠ same type
ACSBG2 p.Ala336Pro Uncertain significance ★ ⚠ same type
ACSBG2 p.Ala336Thr Uncertain significance ★ ⚠ same type
ACSBG2 p.Ala406Asp Uncertain significance ★ ⚠ same type
ACSBG2 p.Ala406Thr Uncertain significance ★ ⚠ same type
ACSBG2 p.Ala543Thr 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/acsbg2-p-pro601arg (accessed [today's date]).

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