Is AGMAT p.Phe116Val (c.346T>G) pathogenic?

AGMAT p.Phe116Val (c.346T>G) is classified Uncertain significance in AGMAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: ambiguous (0.4543); Very rare (popmax 0.000593%, nfe).

How common is AGMAT p.Phe116Val (c.346T>G) in the general population?

AGMAT p.Phe116Val (c.346T>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about AGMAT p.Phe116Val (c.346T>G)?

AlphaMissense predicts ambiguous (score 0.4543) — an in-silico prediction, not a clinical call.

AGMAT p.Phe116Val

c.346T>G · VCV3842437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4543 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4543	ambiguous
REVEL	0.517	indeterminate
SaProt	LLR -11.65	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.99 · regional, not allelic
Overall
CADD	27.2	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 0.000593% European (non-Finnish) · 7/1,180,024 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,461,878 alleles · very rare

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: AGMAT
Protein: p.Phe116Val
Coding: c.346T>G
MANE Select: NM_024758
Type: single nucleotide variant
Location: chr1:15583322 (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-phe116val (accessed [today's date]).

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