Is PYGB p.Ser752Phe (c.2255C>T) pathogenic?

PYGB p.Ser752Phe (c.2255C>T) is classified Uncertain significance in PYGB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: ambiguous (0.4979); Absent from gnomAD v4.1.

How common is PYGB p.Ser752Phe (c.2255C>T) in the general population?

PYGB p.Ser752Phe (c.2255C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYGB p.Ser752Phe (c.2255C>T)?

AlphaMissense predicts ambiguous (score 0.4979) — an in-silico prediction, not a clinical call.

PYGB p.Ser752Phe

c.2255C>T · rs200213744 · VCV3150197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4979	ambiguous
REVEL	0.842	moderately pathogenic-leaning
SaProt	LLR -12.40	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 48 kb · p 0.44 · regional, not allelic
Overall
CADD	24.5	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: PYGB
Protein: p.Ser752Phe
Coding: c.2255C>T
MANE Select: NM_002862
dbSNP: rs200213744
Type: single nucleotide variant
Location: chr20:25294235 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.71 · 2 PDB

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

Similar variants

PYGB p.Ala57Gly Likely benign ★★ same type
PYGB p.Val415= Benign ★★ same type
PYGB p.Ala180Gly Uncertain significance ★ ⚠ same type
PYGB p.Ala247Ser Uncertain significance ★ ⚠ same type
PYGB p.Ala249Val Uncertain significance ★ ⚠ same type
PYGB p.Ala302Thr Uncertain significance ★ ⚠ same type
PYGB p.Ala406Ser Uncertain significance ★ ⚠ same type
PYGB p.Ala611Val Uncertain significance ★ ⚠ 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/pygb-p-ser752phe (accessed [today's date]).

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