Is PHIP p.Arg1571Ser (c.4713G>C) pathogenic?

PHIP p.Arg1571Ser (c.4713G>C) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-26). AlphaMissense: likely benign (0.1956); Absent from gnomAD v4.1; Associated with PHIP-related disorder.

What condition is associated with PHIP p.Arg1571Ser (c.4713G>C)?

PHIP p.Arg1571Ser (c.4713G>C) is associated with PHIP-related disorder (ClinVar).

How common is PHIP p.Arg1571Ser (c.4713G>C) in the general population?

PHIP p.Arg1571Ser (c.4713G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Arg1571Ser (c.4713G>C)?

AlphaMissense predicts likely benign (score 0.1956) — an in-silico prediction, not a clinical call.

PHIP p.Arg1571Ser

c.4713G>C · rs2481789124 · VCV2632299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PHIP-related disorder

⚠ 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	0.1956	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.27	GERP -0.67, phastCons 0.98
Regional constraint	o/e 0.94	unconstrained · MANE · 5,311 bp · p 0.29 · regional, not allelic
Overall
CADD	16.9	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.

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.Arg1571Ser
Coding: c.4713G>C
MANE Select: NM_017934
dbSNP: rs2481789124
Type: single nucleotide variant
Location: chr6:78945415 (GRCh38)

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

Disease context

PHIP-related disorder

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-arg1571ser (accessed [today's date]).

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