Is AEBP1 p.Arg595Ter (c.1783C>T) pathogenic?

AEBP1 p.Arg595Ter (c.1783C>T) is classified Pathogenic in AEBP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00446%, eas).

How common is AEBP1 p.Arg595Ter (c.1783C>T) in the general population?

AEBP1 p.Arg595Ter (c.1783C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

AEBP1 p.Arg595Ter

c.1783C>T · rs1168034376 · VCV1676869

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 21
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.8, phastCons 0.9
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00062% 10/1,612,962 alleles · very rare exomes 10/1,460,702 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
Remaining individualsnot grpmax-eligible	0.0016%	62,450
European (non-Finnish)	0.000593%	168,507

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: AEBP1
Protein: p.Arg595Ter
Coding: c.1783C>T
MANE Select: NM_001129
dbSNP: rs1168034376
Type: single nucleotide variant
Location: chr7:44111573 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 595: a UniProt-annotated variant site (in edscll2); the peptidase m14 domain; the 'interaction with mapk1 and mapk3' region; the 'interaction with pten' region

Full AEBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AEBP1 p.Arg595Gln Uncertain significance ★ ⚠ same residue
AEBP1 c.1018+1G>A Likely pathogenic ★★ same type
AEBP1 c.1630+1G>A Pathogenic ★★ same type
AEBP1 c.1630+2T>A Pathogenic ★★ same type
AEBP1 p.Cys581Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Cys868Ter Likely pathogenic ★★ same type
AEBP1 p.Gln781Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Tyr428Ter Pathogenic/Likely pathogenic ★★ 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/aebp1-p-arg595ter (accessed [today's date]).

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