Is PHIP p.Pro1293Ser (c.3877C>T) pathogenic?

PHIP p.Pro1293Ser (c.3877C>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). AlphaMissense: likely pathogenic (0.7729); Absent from gnomAD v4.1; Associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome.

How common is PHIP p.Pro1293Ser (c.3877C>T) in the general population?

PHIP p.Pro1293Ser (c.3877C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Pro1293Ser (c.3877C>T)?

AlphaMissense predicts likely pathogenic (score 0.7729) — an in-silico prediction, not a clinical call.

PHIP p.Pro1293Ser

Q: What condition is associated with PHIP p.Pro1293Ser (c.3877C>T)?

PHIP p.Pro1293Ser (c.3877C>T) is associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (ClinVar).

Q: How is PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.3877C>T · VCV4056717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.7729	likely pathogenic
REVEL	0.307	indeterminate
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 9,095 bp · p 7e-13 · regional, not allelic
Overall
CADD	27.1	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: PHIP
Protein: p.Pro1293Ser
Coding: c.3877C>T
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:78955258 (GRCh38)

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

Disease context

For PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Infancy, Neonatal

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/phip-p-pro1293ser (accessed [today's date]).

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