Is ASB3 p.Asp294Gly (c.881A>G) pathogenic?

ASB3 p.Asp294Gly (c.881A>G) is classified Uncertain significance in ASB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0771); Ultra-rare (popmax 0.0152%, nfe).

How common is ASB3 p.Asp294Gly (c.881A>G) in the general population?

ASB3 p.Asp294Gly (c.881A>G) is ultra-rare (popmax 0.0152%, nfe) (gnomAD).

What do computational predictors say about ASB3 p.Asp294Gly (c.881A>G)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

ASB3 p.Asp294Gly

c.881A>G · rs750182921 · VCV2602559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.52	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 1.9	GERP -1.2, phastCons 0.036
Regional constraint	o/e 1.18	unconstrained · MANE · 95 kb · p 5.6e-06 · regional, not allelic
Overall
CADD	21.6	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 0.0152% European (non-Finnish) · 179/1,180,036 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0126%

Overall 0.0118% 191/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.0152%	6,592
African / African-American	0.00133%	74,952

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASB3
Protein: p.Asp294Gly
Coding: c.881A>G
MANE Select: NM_016115
dbSNP: rs750182921
Type: single nucleotide variant
Location: chr2:53714483 (GRCh38)
Gene constraint: LOEUF 0.998 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.62

Full ASB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB3 p.Gln309Arg Uncertain significance ★ ⚠ same type
CHAC2 p.Ala149Gly Uncertain significance ★ ⚠ same type
CHAC2 p.Ala64Thr Uncertain significance ★ ⚠ same type
CHAC2 p.Arg174Cys Uncertain significance ★ ⚠ same type
CHAC2 p.Arg174His Uncertain significance ★ ⚠ same type
CHAC2 p.Arg40His Uncertain significance ★ ⚠ same type
CHAC2 p.Asn154Lys Uncertain significance ★ ⚠ same type
CHAC2 p.Asn180His 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/asb3-p-asp294gly (accessed [today's date]).

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