Is UGGT1 p.Pro144Ala (c.430C>G) pathogenic?

UGGT1 p.Pro144Ala (c.430C>G) is classified Uncertain significance in UGGT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). AlphaMissense: likely benign (0.1401); Absent from gnomAD v4.1.

How common is UGGT1 p.Pro144Ala (c.430C>G) in the general population?

UGGT1 p.Pro144Ala (c.430C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UGGT1 p.Pro144Ala (c.430C>G)?

AlphaMissense predicts likely benign (score 0.1401) — an in-silico prediction, not a clinical call.

UGGT1 p.Pro144Ala

c.430C>G · rs2467304469 · VCV2336195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1401	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 0.86, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.86 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: UGGT1
Protein: p.Pro144Ala
Coding: c.430C>G
MANE Select: NM_020120
dbSNP: rs2467304469
Type: single nucleotide variant
Location: chr2:128109655 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.97

Full UGGT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UGGT1 p.Glu918Lys Uncertain significance ★★ ⚠ same type
UGGT1 p.Pro1126Leu Uncertain significance ★★ ⚠ same type
UGGT1 c.278-9C>T Benign ★★ same type
UGGT1 c.3025-4C>T Benign/Likely benign ★★ same type
UGGT1 c.4643-8T>G Benign ★★ same type
UGGT1 p.Ala669Val Benign ★★ same type
UGGT1 p.Asn1139Ser Benign ★★ same type
UGGT1 p.Glu422= Benign ★★ 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/uggt1-p-pro144ala (accessed [today's date]).

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