Is AGBL5 p.Arg271Gln (c.812G>A) pathogenic?

AGBL5 p.Arg271Gln (c.812G>A) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely benign (0.1334); Very rare (popmax 0.00445%, eas).

How common is AGBL5 p.Arg271Gln (c.812G>A) in the general population?

AGBL5 p.Arg271Gln (c.812G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about AGBL5 p.Arg271Gln (c.812G>A)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

AGBL5 p.Arg271Gln

c.812G>A · rs754070994 · VCV1350414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00445% East Asian · 2/44,900 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000496% 8/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,450
South Asian	0.0022%	45,543
European (non-Finnish)	0.000339%	295,008

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: AGBL5
Protein: p.Arg271Gln
Coding: c.812G>A
MANE Select: NM_021831
dbSNP: rs754070994
Type: single nucleotide variant
Location: chr2:27055157 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 271: the peptidase m14 domain; a UniProt-annotated variant site (found in patients with a usher-like phenotype encompassing rp and hearing loss; likely pathogenic)

Full AGBL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGBL5 p.Arg220Ter Pathogenic ★★ same type
AGBL5 p.Arg487Ter Pathogenic ★★ same type
AGBL5 p.Trp592Ter Pathogenic ★★ same type
AGBL5 p.Tyr485Ter Pathogenic/Likely pathogenic ★★ same type
AGBL5 c.2355+4A>G Uncertain significance ★★ same type
AGBL5 c.551+5C>A Uncertain significance ★★ same type
AGBL5 p.Ala530Thr Uncertain significance ★★ ⚠ same type
AGBL5 p.Ala570Val 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/agbl5-p-arg271gln (accessed [today's date]).

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