Is PHIP p.Arg799Ser (c.2397A>T) pathogenic?

PHIP p.Arg799Ser (c.2397A>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-15). AlphaMissense: likely pathogenic (0.9966); Absent from gnomAD v4.1.

How common is PHIP p.Arg799Ser (c.2397A>T) in the general population?

PHIP p.Arg799Ser (c.2397A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Arg799Ser (c.2397A>T)?

AlphaMissense predicts likely pathogenic (score 0.9966) — an in-silico prediction, not a clinical call.

PHIP p.Arg799Ser

c.2397A>T · rs2127721787 · VCV1307750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9966	likely pathogenic · top 9% in PHIP
REVEL	0.354	indeterminate
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP 0.083, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 5,581 bp · p 0.29 · regional, not allelic
Overall
CADD	22.9	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.Arg799Ser
Coding: c.2397A>T
MANE Select: NM_017934
dbSNP: rs2127721787
Type: single nucleotide variant
Location: chr6:78988272 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 799: the 'disordered' region; a UniProt-annotated variant site (in chujans)

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

Similar variants

PHIP p.Arg799Ile Uncertain significance ★★ ⚠ same residue
PHIP p.Arg110Cys Pathogenic/Likely pathogenic ★★ same type
PHIP p.Arg178Ter Pathogenic/Likely pathogenic ★★ same type
PHIP p.Arg193Ter Pathogenic ★★ same type
PHIP p.Arg255Ter Pathogenic/Likely pathogenic ★★ same type
PHIP p.Arg396Ter Pathogenic/Likely pathogenic ★★ same type
PHIP p.Arg503Ter Pathogenic/Likely pathogenic ★★ same type
PHIP p.Arg721Ter Pathogenic/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/phip-p-arg799ser (accessed [today's date]).

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