Is PHIP p.Arg37Cys (c.109C>T) pathogenic?

PHIP p.Arg37Cys (c.109C>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.418); Very rare (popmax 0.000118%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PHIP p.Arg37Cys (c.109C>T)?

PHIP p.Arg37Cys (c.109C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHIP p.Arg37Cys (c.109C>T) in the general population?

PHIP p.Arg37Cys (c.109C>T) is very rare (popmax 0.000118%, nfe) (gnomAD).

What do computational predictors say about PHIP p.Arg37Cys (c.109C>T)?

AlphaMissense predicts ambiguous (score 0.418) — an in-silico prediction, not a clinical call.

PHIP p.Arg37Cys

c.109C>T · VCV4135819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000118%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.418	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.23, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 572 bp · p 0.14 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.000118% European (non-Finnish) · 1/850,296 alleles

Overall 9.87e-05% 1/1,013,304 alleles · very rare exomes 1/869,318 · genomes 0/143,986 · 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.Arg37Cys
Coding: c.109C>T
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:79077720 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHIP p.Arg37= Likely benign same residue
PHIP p.Arg160Gly Uncertain significance ★★ ⚠ same condition
PHIP p.Arg346Gln Uncertain significance ★★ ⚠ same condition
PHIP p.Arg691Leu Uncertain significance ★★ ⚠ same condition
PHIP p.Arg799Ile Uncertain significance ★★ ⚠ same condition
PHIP p.Arg837Thr Uncertain significance ★★ ⚠ same condition
PHIP p.Asn795His Uncertain significance ★★ ⚠ same condition
PHIP p.Gln638Glu Uncertain significance ★★ ⚠ same condition

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-arg37cys (accessed [today's date]).

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