Is PHIP p.Arg601Ser (c.1803A>T) pathogenic?

PHIP p.Arg601Ser (c.1803A>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-28). AlphaMissense: ambiguous (0.4045); Very rare (popmax 0.000933%, nfe).

How common is PHIP p.Arg601Ser (c.1803A>T) in the general population?

PHIP p.Arg601Ser (c.1803A>T) is very rare (popmax 0.000933%, nfe) (gnomAD).

What do computational predictors say about PHIP p.Arg601Ser (c.1803A>T)?

AlphaMissense predicts ambiguous (score 0.4045) — an in-silico prediction, not a clinical call.

PHIP p.Arg601Ser

c.1803A>T · VCV4746744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4045	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -10.46	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP -0.47, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 11 kb · p 7.6e-13 · regional, not allelic
Overall
CADD	22.6	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

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,496 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,310 alleles · very rare exomes 11/1,461,182 · genomes 0/152,128 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PHIP
Protein: p.Arg601Ser
Coding: c.1803A>T
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:79001975 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 601: 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.Arg601Ile 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-arg601ser (accessed [today's date]).

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