Is AEBP2 p.His395Arg (c.1184A>G) pathogenic?

AEBP2 p.His395Arg (c.1184A>G) is classified Uncertain significance in AEBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-07). AlphaMissense: likely pathogenic (0.798); Very rare (popmax 0.00225%, sas).

How common is AEBP2 p.His395Arg (c.1184A>G) in the general population?

AEBP2 p.His395Arg (c.1184A>G) is very rare (popmax 0.00225%, sas) (gnomAD).

What do computational predictors say about AEBP2 p.His395Arg (c.1184A>G)?

AlphaMissense predicts likely pathogenic (score 0.798) — an in-silico prediction, not a clinical call.

AEBP2 p.His395Arg

c.1184A>G · VCV4246610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.798 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00225%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.798	likely pathogenic
REVEL	0.652	pathogenic-leaning
SaProt	LLR -7.96	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 78 kb · p 4.6e-19 · regional, not allelic
Overall
CADD	26.8	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 0.00225% South Asian · 2/88,946 alleles

Filtering AF 0.000373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00014%

Overall 0.000311% 5/1,605,728 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00225%	44,473
European (non-Finnish)	0.000255%	392,115

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.His395Arg
Coding: c.1184A>G
MANE Select: NM_153207
Type: single nucleotide variant
Location: chr12:19500106 (GRCh38)
Gene constraint: LOEUF 0.461 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.62 · 21 PDB

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

Similar variants

AEBP2 p.His395Tyr 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-his395arg (accessed [today's date]).

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