Is POU2F2 p.Ser477Pro (c.1429T>C) pathogenic?

POU2F2 p.Ser477Pro (c.1429T>C) is classified Uncertain significance in POU2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). AlphaMissense: likely benign (0.0999); Absent from gnomAD v4.1.

How common is POU2F2 p.Ser477Pro (c.1429T>C) in the general population?

POU2F2 p.Ser477Pro (c.1429T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about POU2F2 p.Ser477Pro (c.1429T>C)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

POU2F2 p.Ser477Pro

c.1429T>C · VCV3423214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.71, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,048 bp · p 0.032 · regional, not allelic
Overall
CADD	24.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S455P vs ClinVar S477P) — verify the residue.

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: POU2F2
Protein: p.Ser477Pro
Coding: c.1429T>C
MANE Select: NM_001394376
Type: single nucleotide variant
Location: chr19:42092106 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.37 · 2 PDB
Residue 455 UniProt numbering: the 'disordered' region

Full POU2F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

POU2F2 p.Ser477Leu Uncertain significance ★ ⚠ same residue
POU2F2 p.Ala184Thr Uncertain significance ★ ⚠ same type
POU2F2 p.Ala406Thr Uncertain significance ★ ⚠ same type
POU2F2 p.Ala406Val Uncertain significance ★ ⚠ same type
POU2F2 p.Arg436Trp Uncertain significance ★ ⚠ same type
POU2F2 p.Asn452Ser Uncertain significance ★ ⚠ same type
POU2F2 p.Asn485Asp Uncertain significance ★ ⚠ same type
POU2F2 p.Asp289Asn 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/pou2f2-p-ser477pro (accessed [today's date]).

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