Is GAMT p.Ser173Phe (c.518C>T) pathogenic?

GAMT p.Ser173Phe (c.518C>T) is classified Uncertain significance in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-16). AlphaMissense: likely pathogenic (0.9607); Absent from gnomAD v4.1.

How common is GAMT p.Ser173Phe (c.518C>T) in the general population?

GAMT p.Ser173Phe (c.518C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GAMT p.Ser173Phe (c.518C>T)?

AlphaMissense predicts likely pathogenic (score 0.9607) — an in-silico prediction, not a clinical call.

GAMT p.Ser173Phe

c.518C>T · rs2144636300 · VCV1303300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9607	likely pathogenic · top 8% in GAMT
REVEL	0.745	pathogenic-leaning
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,114 bp · p 0.00031 · regional, not allelic
Overall
CADD	32.0	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: GAMT
Protein: p.Ser173Phe
Coding: c.518C>T
MANE Select: NM_000156
dbSNP: rs2144636300
Type: single nucleotide variant
Location: chr19:1398968 (GRCh38)
Gene constraint: LOEUF 1.536 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.73 · 1 PDB
Residue 173: the rmt2 domain; an α-helix

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

Similar variants

GAMT p.Ser173= Likely benign ★ same residue
GAMT p.Ser173Thr Uncertain significance ⚠ same residue
GAMT c.327+43G>A Likely pathogenic ★★★ same type
GAMT c.328-1G>A Pathogenic ★★★ same type
GAMT c.328-2A>G Pathogenic ★★★ same type
GAMT c.391+15G>T Likely pathogenic ★★★ same type
GAMT c.391+1G>C Pathogenic ★★★ same type
GAMT c.391+5G>C Likely pathogenic ★★★ 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/gamt-p-ser173phe (accessed [today's date]).

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