Is EBAG9 p.Asp136Tyr (c.406G>T) pathogenic?

EBAG9 p.Asp136Tyr (c.406G>T) is classified Uncertain significance in EBAG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.7856); Ultra-rare (popmax 0.0167%, mid).

How common is EBAG9 p.Asp136Tyr (c.406G>T) in the general population?

EBAG9 p.Asp136Tyr (c.406G>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about EBAG9 p.Asp136Tyr (c.406G>T)?

AlphaMissense predicts likely pathogenic (score 0.7856) — an in-silico prediction, not a clinical call.

EBAG9 p.Asp136Tyr

c.406G>T · VCV4662842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7856	likely pathogenic
REVEL	0.582	indeterminate
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 0.0038 · regional, not allelic
Overall
CADD	29.6	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 0.0167% Middle Eastern · 1/5,994 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000206% 3/1,454,188 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,994
African / African-American	0.00267%	37,400

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.Asp136Tyr
Coding: c.406G>T
MANE Select: NM_004215
Type: single nucleotide variant
Location: chr8:109557019 (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.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-asp136tyr (accessed [today's date]).

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