Is AEBP2 p.Ser83Trp (c.248C>G) pathogenic?

AEBP2 p.Ser83Trp (c.248C>G) is classified Uncertain significance in AEBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.4508); Ultra-rare (popmax 0.0127%, nfe).

How common is AEBP2 p.Ser83Trp (c.248C>G) in the general population?

AEBP2 p.Ser83Trp (c.248C>G) is ultra-rare (popmax 0.0127%, nfe) (gnomAD).

What do computational predictors say about AEBP2 p.Ser83Trp (c.248C>G)?

AlphaMissense predicts ambiguous (score 0.4508) — an in-silico prediction, not a clinical call.

AEBP2 p.Ser83Trp

c.248C>G · rs1286268721 · VCV2545116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4508 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0127%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4508	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -10.32	damaging
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	23.6	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 0.0127% European (non-Finnish) · 145/1,138,536 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00991% 150/1,513,512 alleles · ultra-rare exomes 138/1,364,254 · genomes 12/149,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0127%	7,852
Remaining individualsnot grpmax-eligible	0.00339%	29,508
African / African-American	0.00291%	34,314
Finnishnot grpmax-eligible	0.00225%	44,452

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.Ser83Trp
Coding: c.248C>G
MANE Select: NM_153207
dbSNP: rs1286268721
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.Ser83Leu 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-ser83trp (accessed [today's date]).

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