Is AGMAT p.Leu255Pro (c.764T>C) pathogenic?

AGMAT p.Leu255Pro (c.764T>C) is classified Uncertain significance in AGMAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: ambiguous (0.4648); Absent from gnomAD v4.1.

How common is AGMAT p.Leu255Pro (c.764T>C) in the general population?

AGMAT p.Leu255Pro (c.764T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGMAT p.Leu255Pro (c.764T>C)?

AlphaMissense predicts ambiguous (score 0.4648) — an in-silico prediction, not a clinical call.

AGMAT p.Leu255Pro

c.764T>C · VCV3842429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4648	ambiguous
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -16.05	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.99 · regional, not allelic
Overall
CADD	28.5	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

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: AGMAT
Protein: p.Leu255Pro
Coding: c.764T>C
MANE Select: NM_024758
Type: single nucleotide variant
Location: chr1:15577821 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.12

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

Similar variants

AGMAT p.Thr229Met Benign ★★ same type
AGMAT p.Thr351= Benign ★★ same type
AGMAT p.Ala10Ser Uncertain significance ★ ⚠ same type
AGMAT p.Ala113Asp Uncertain significance ★ ⚠ same type
AGMAT p.Ala186Val Uncertain significance ★ ⚠ same type
AGMAT p.Ala285Val Uncertain significance ★ ⚠ same type
AGMAT p.Ala335Val Uncertain significance ★ ⚠ same type
AGMAT p.Ala74Ser 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/agmat-p-leu255pro (accessed [today's date]).

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