Is AGBL5 p.Val25Ala (c.74T>C) pathogenic?

AGBL5 p.Val25Ala (c.74T>C) is classified Uncertain significance in AGBL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). AlphaMissense: ambiguous (0.4663); Absent from gnomAD v4.1.

How common is AGBL5 p.Val25Ala (c.74T>C) in the general population?

AGBL5 p.Val25Ala (c.74T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGBL5 p.Val25Ala (c.74T>C)?

AlphaMissense predicts ambiguous (score 0.4663) — an in-silico prediction, not a clinical call.

AGBL5 p.Val25Ala

c.74T>C · rs2148267429 · VCV1409712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4663	ambiguous
REVEL	0.739	pathogenic-leaning
SaProt	LLR -8.36	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,357 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGBL5
Protein: p.Val25Ala
Coding: c.74T>C
MANE Select: NM_021831
dbSNP: rs2148267429
Type: single nucleotide variant
Location: chr2:27053032 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.36 · 10 PDB
Residue 25: a β-strand

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-val25ala (accessed [today's date]).

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