Is EBAG9 p.Arg33Trp (c.97C>T) pathogenic?

EBAG9 p.Arg33Trp (c.97C>T) is classified Uncertain significance in EBAG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely pathogenic (0.8862); Ultra-rare (popmax 0.0309%, afr).

How common is EBAG9 p.Arg33Trp (c.97C>T) in the general population?

EBAG9 p.Arg33Trp (c.97C>T) is ultra-rare (popmax 0.0309%, afr) (gnomAD).

What do computational predictors say about EBAG9 p.Arg33Trp (c.97C>T)?

AlphaMissense predicts likely pathogenic (score 0.8862) — an in-silico prediction, not a clinical call.

EBAG9 p.Arg33Trp

c.97C>T · rs199580138 · VCV2521364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8862	likely pathogenic
REVEL	0.528	indeterminate
SaProt	LLR -12.49	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.45, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 0.0038 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0309% African / African-American · 23/74,468 alleles

Filtering AF 0.0211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00243% 39/1,606,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0309%	3,238
Remaining individualsnot grpmax-eligible	0.00161%	62,218
European (non-Finnish)	0.00119%	84,123
South Asian	0.00113%	88,698

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: EBAG9
Protein: p.Arg33Trp
Coding: c.97C>T
MANE Select: NM_004215
dbSNP: rs199580138
Type: single nucleotide variant
Location: chr8:109553878 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 66.63

Full EBAG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBAG9 c.162+5G>T Benign ★★ same type
EBAG9 p.Ala2Thr Uncertain significance ★ ⚠ same type
EBAG9 p.Arg199Gln Uncertain significance ★ ⚠ same type
EBAG9 p.Arg28Gly Uncertain significance ★ ⚠ same type
EBAG9 p.Arg7Gln Uncertain significance ★ ⚠ same type
EBAG9 p.Asp122Glu Uncertain significance ★ ⚠ same type
EBAG9 p.Asp136Tyr Uncertain significance ★ ⚠ same type
EBAG9 p.Asp56Ala 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/ebag9-p-arg33trp (accessed [today's date]).

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