Is AGBL4 p.Arg348Gln (c.1043G>A) pathogenic?

AGBL4 p.Arg348Gln (c.1043G>A) is classified Uncertain significance in AGBL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: ambiguous (0.352); Ultra-rare (popmax 0.012%, afr).

How common is AGBL4 p.Arg348Gln (c.1043G>A) in the general population?

AGBL4 p.Arg348Gln (c.1043G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about AGBL4 p.Arg348Gln (c.1043G>A)?

AlphaMissense predicts ambiguous (score 0.352) — an in-silico prediction, not a clinical call.

AGBL4 p.Arg348Gln

c.1043G>A · rs899125154 · VCV2292499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.352 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.352	ambiguous
REVEL	0.157	moderately benign-leaning
SaProt	LLR -13.78	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.081, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 1,490 kb · p 0.038 · regional, not allelic
Overall
CADD	26.5	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 0.012% African / African-American · 9/74,846 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00112% 18/1,608,262 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,316
Admixed American	0.00168%	59,368
South Asian	0.00112%	89,190
European (non-Finnish)	0.000594%	168,222

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.Arg348Gln
Coding: c.1043G>A
MANE Select: NM_032785
dbSNP: rs899125154
Type: single nucleotide variant
Location: chr1:48590894 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.59
Residue 348: the peptidase m14 domain

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

Similar variants

AGBL4 p.Arg348Trp Uncertain significance ★ ⚠ same residue
AGBL4 p.Ala480Gly Uncertain significance ★ ⚠ same type
AGBL4 p.Ala480Val Uncertain significance ★ ⚠ same type
AGBL4 p.Arg258Gln 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
AGBL4 p.Arg385Gly 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-arg348gln (accessed [today's date]).

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