Is UBE2A p.Phe77Ser (c.230T>C) pathogenic?

UBE2A p.Phe77Ser (c.230T>C) is classified Uncertain significance in UBE2A (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-01). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1.

How common is UBE2A p.Phe77Ser (c.230T>C) in the general population?

UBE2A p.Phe77Ser (c.230T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBE2A p.Phe77Ser (c.230T>C)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

UBE2A p.Phe77Ser

c.230T>C · rs2147380344 · VCV1306501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 8% in UBE2A
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -15.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 8,540 bp · p 1.2e-18 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: UBE2A
Protein: p.Phe77Ser
Coding: c.230T>C
MANE Select: NM_003336
dbSNP: rs2147380344
Type: single nucleotide variant
Location: chrX:119581585 (GRCh38)
Structure: AlphaFold pLDDT 94.25 · 5 PDB
Residue 77: the ubc core domain

Full UBE2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBE2A p.Arg135Trp Uncertain significance ★★ ⚠ same type
UBE2A p.Arg95Cys Uncertain significance ★★ ⚠ same type
UBE2A p.Ile57Val Uncertain significance ★★ ⚠ same type
UBE2A c.125+14C>T Benign/Likely benign ★★ same type
UBE2A c.44+8G>A Likely benign ★★ same type
UBE2A c.45-5C>T Benign/Likely benign ★★ same type
UBE2A p.Thr107= Benign/Likely benign ★★ same type
UBE2A c.125+1G>T 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/ube2a-p-phe77ser (accessed [today's date]).

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