Is AEBP2 p.Phe328Ser (c.983T>C) pathogenic?

AEBP2 p.Phe328Ser (c.983T>C) is classified Uncertain significance in AEBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely pathogenic (0.9999); Very rare (popmax 9.57e-05%, nfe).

How common is AEBP2 p.Phe328Ser (c.983T>C) in the general population?

AEBP2 p.Phe328Ser (c.983T>C) is very rare (popmax 9.57e-05%, nfe) (gnomAD).

What do computational predictors say about AEBP2 p.Phe328Ser (c.983T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

AEBP2 p.Phe328Ser

c.983T>C · rs2497682898 · VCV2254652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.57e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 5% in AEBP2
REVEL	0.587	indeterminate
SaProt	LLR -11.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 78 kb · p 4.6e-19 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 9.57e-05% European (non-Finnish) · 1/1,045,302 alleles

Overall 8.02e-05% 1/1,247,524 alleles · very rare

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.Phe328Ser
Coding: c.983T>C
MANE Select: NM_153207
dbSNP: rs2497682898
Type: single nucleotide variant
Location: chr12:19473351 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 21 PDB
Residue 328: a β-strand

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

Similar variants

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
AEBP2 p.Asn336Ser 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-phe328ser (accessed [today's date]).

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