Is AGBL4 p.Pro131His (c.392C>A) pathogenic?

AGBL4 p.Pro131His (c.392C>A) is classified Uncertain significance in AGBL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.2527); Ultra-rare (popmax 0.0342%, eas).

How common is AGBL4 p.Pro131His (c.392C>A) in the general population?

AGBL4 p.Pro131His (c.392C>A) is ultra-rare (popmax 0.0342%, eas) (gnomAD).

What do computational predictors say about AGBL4 p.Pro131His (c.392C>A)?

AlphaMissense predicts likely benign (score 0.2527) — an in-silico prediction, not a clinical call.

AGBL4 p.Pro131His

c.392C>A · VCV3275656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2527 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2527	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,490 kb · p 0.038 · regional, not allelic
Overall
CADD	25.0	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 0.0342% East Asian · 14/40,914 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0029% 45/1,551,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0342%	2,922
South Asian	0.025%	3,999
Remaining individualsnot grpmax-eligible	0.00166%	60,116
African / African-American	0.00137%	73,104
European (non-Finnish)	0.000698%	143,318

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: AGBL4
Protein: p.Pro131His
Coding: c.392C>A
MANE Select: NM_032785
Type: single nucleotide variant
Location: chr1:49045786 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.59

Full AGBL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGBL4 p.Ala480Gly Uncertain significance ★ ⚠ same type
AGBL4 p.Ala480Val Uncertain significance ★ ⚠ same type
AGBL4 p.Arg258Gln Uncertain significance ★ ⚠ same type
AGBL4 p.Arg348Gln Uncertain significance ★ ⚠ same type
AGBL4 p.Arg348Trp Uncertain significance ★ ⚠ same type
AGBL4 p.Arg351Ser Uncertain significance ★ ⚠ same type
AGBL4 p.Arg375Trp Uncertain significance ★ ⚠ same type
AGBL4 p.Arg385Cys 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/agbl4-p-pro131his (accessed [today's date]).

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