Is EBAG9 p.Leu35Ser (c.104T>C) pathogenic?

EBAG9 p.Leu35Ser (c.104T>C) is classified Uncertain significance in EBAG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely pathogenic (0.8418); Absent from gnomAD v4.1.

How common is EBAG9 p.Leu35Ser (c.104T>C) in the general population?

EBAG9 p.Leu35Ser (c.104T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EBAG9 p.Leu35Ser (c.104T>C)?

AlphaMissense predicts likely pathogenic (score 0.8418) — an in-silico prediction, not a clinical call.

EBAG9 p.Leu35Ser

c.104T>C · VCV4015906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8418	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -10.80	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 0.0038 · regional, not allelic
Overall
CADD	23.3	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: EBAG9
Protein: p.Leu35Ser
Coding: c.104T>C
MANE Select: NM_004215
Type: single nucleotide variant
Location: chr8:109553885 (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.Arg33Trp 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

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-leu35ser (accessed [today's date]).

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