Is EBLN2 p.Ala90Ser (c.268G>T) pathogenic?

EBLN2 p.Ala90Ser (c.268G>T) is classified Uncertain significance in EBLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1046); Low-frequency (popmax 1.29%, eas).

How common is EBLN2 p.Ala90Ser (c.268G>T) in the general population?

EBLN2 p.Ala90Ser (c.268G>T) is low-frequency (popmax 1.29%, eas) (gnomAD).

What do computational predictors say about EBLN2 p.Ala90Ser (c.268G>T)?

AlphaMissense predicts likely benign (score 0.1046) — an in-silico prediction, not a clinical call.

EBLN2 p.Ala90Ser

c.268G>T · VCV4246287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1046 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.29%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1046	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.3	GERP 0.19
Regional constraint	o/e 1.22	unconstrained · MANE · 815 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	8.206	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 1.29% East Asian · 580/44,814 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 0.0375% 602/1,607,180 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.29%	77
Remaining individualsnot grpmax-eligible	0.0241%	4,145
Ashkenazi Jewishnot grpmax-eligible	0.0171%	5,862
European (non-Finnish)	0.00017%	588,956

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: EBLN2
Protein: p.Ala90Ser
Coding: c.268G>T
MANE Select: NM_018029
Type: single nucleotide variant
Location: chr3:73062349 (GRCh38)

Full EBLN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ebln2-p-ala90ser (accessed [today's date]).

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