Is ACSBG2 p.Phe394Ser (c.1181T>C) pathogenic?

ACSBG2 p.Phe394Ser (c.1181T>C) is classified Uncertain significance in ACSBG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: ambiguous (0.3675); Absent from gnomAD v4.1.

How common is ACSBG2 p.Phe394Ser (c.1181T>C) in the general population?

ACSBG2 p.Phe394Ser (c.1181T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSBG2 p.Phe394Ser (c.1181T>C)?

AlphaMissense predicts ambiguous (score 0.3675) — an in-silico prediction, not a clinical call.

ACSBG2 p.Phe394Ser

c.1181T>C · VCV4000199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3675 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3675	ambiguous
REVEL	0.129	moderately benign-leaning
SaProt	LLR -12.91	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.015	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 49 kb · p 0.0022 · regional, not allelic
Overall
CADD	11.89	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACSBG2
Protein: p.Phe394Ser
Coding: c.1181T>C
MANE Select: NM_030924
Type: single nucleotide variant
Location: chr19:6183131 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.67

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.Pro601Arg 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

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-phe394ser (accessed [today's date]).

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