Is AEBP2 p.Ser83Leu (c.248C>T) pathogenic?

AEBP2 p.Ser83Leu (c.248C>T) is classified Uncertain significance in AEBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1909); Very rare (popmax 0.00267%, eas).

How common is AEBP2 p.Ser83Leu (c.248C>T) in the general population?

AEBP2 p.Ser83Leu (c.248C>T) is very rare (popmax 0.00267%, eas) (gnomAD).

What do computational predictors say about AEBP2 p.Ser83Leu (c.248C>T)?

AlphaMissense predicts likely benign (score 0.1909) — an in-silico prediction, not a clinical call.

AEBP2 p.Ser83Leu

c.248C>T · VCV3839549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1909	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.57	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 5.3	GERP 1.2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 659 bp · p 0.0074 · regional, not allelic
Overall
CADD	23.2	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 0.00267% East Asian · 1/37,432 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000198% 3/1,513,512 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00267%	37,432
European (non-Finnish)	0.000176%	569,269

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: AEBP2
Protein: p.Ser83Leu
Coding: c.248C>T
MANE Select: NM_153207
Type: single nucleotide variant
Location: chr12:19439947 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 21 PDB
Residue 83: the 'disordered' region

Full AEBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AEBP2 p.Ser83Trp Uncertain significance ★ ⚠ same residue
AEBP2 p.Ala198Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Ala33Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Ala4Ser Uncertain significance ★ ⚠ same type
AEBP2 p.Arg138Ser Uncertain significance ★ ⚠ same type
AEBP2 p.Arg16Pro Uncertain significance ★ ⚠ same type
AEBP2 p.Asn273Thr Uncertain significance ★ ⚠ same type
AEBP2 p.Asn336Asp 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/aebp2-p-ser83leu (accessed [today's date]).

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