Is UXT p.Ala2Ser (c.4G>T) pathogenic?

UXT p.Ala2Ser (c.4G>T) is classified Uncertain significance in UXT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0135%, amr).

How common is UXT p.Ala2Ser (c.4G>T) in the general population?

UXT p.Ala2Ser (c.4G>T) is ultra-rare (popmax 0.0135%, amr) (gnomAD).

What do computational predictors say about UXT p.Ala2Ser (c.4G>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

UXT p.Ala2Ser

c.4G>T · rs762944503 · VCV2272929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.64, phastCons 1
Overall
CADD	21.0	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

Grpmax group 0.0135% Admixed American · 6/44,605 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.000501% 6/1,197,163 alleles · ultra-rare exomes 2/1,084,055 · genomes 4/113,108 · joint denominator

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: UXT
Protein: p.Ala2Ser
Coding: c.4G>T
MANE Select: NM_004182
dbSNP: rs762944503
Type: single nucleotide variant
Location: chrX:47658924 (GRCh38)
Structure: AlphaFold pLDDT 88.06

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

Similar variants

STAP1 p.Met2Thr Benign same residue
STAP1 p.Gln192Arg Uncertain significance ★★ ⚠ same type
STAP1 p.Leu288Val Uncertain significance ★★ ⚠ same type
STAP1 c.120+6T>C Benign/Likely benign ★★ same type
STAP1 c.192+102T>C Likely benign ★★ same type
STAP1 c.192+10T>C Benign ★★ same type
STAP1 c.530+11A>G Benign ★★ same type
STAP1 c.530+60A>G 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/uxt-p-ala2ser (accessed [today's date]).

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