Is GAMT p.Pro48Ser (c.142C>T) pathogenic?

GAMT p.Pro48Ser (c.142C>T) is classified Uncertain significance in GAMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.2852); No allele count reported in gnomAD v4.1 (AN 1,534,602).

How common is GAMT p.Pro48Ser (c.142C>T) in the general population?

GAMT p.Pro48Ser (c.142C>T) is no allele count reported in gnomAD v4.1 (AN 1,534,602) (gnomAD).

What do computational predictors say about GAMT p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely benign (score 0.2852) — an in-silico prediction, not a clinical call.

GAMT p.Pro48Ser

c.142C>T · rs2144641030 · VCV1304798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2852 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,602)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2852	likely benign
REVEL	0.769	pathogenic-leaning
SaProt	LLR -10.70	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	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

No allele count reported in gnomAD v4.1 (AN 1,534,602). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GAMT
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_000156
dbSNP: rs2144641030
Type: single nucleotide variant
Location: chr19:1401335 (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 48: the rmt2 domain; an α-helix

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

Similar variants

GAMT p.Pro48= Likely benign ★ 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
GAMT p.Ala156Asp 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-pro48ser (accessed [today's date]).

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