Is PHIP p.Arg1441= (c.4321A>C) pathogenic?

PHIP p.Arg1441= (c.4321A>C) is classified Benign/Likely benign in PHIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Rare (popmax 0.79%, amr).

How common is PHIP p.Arg1441= (c.4321A>C) in the general population?

PHIP p.Arg1441= (c.4321A>C) is rare (popmax 0.79%, amr) (gnomAD).

PHIP p.Arg1441=

c.4321A>C · rs148337691 · VCV2046809

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.79%, amr)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.2	GERP 2.9, phastCons 1
Overall
CADD	11.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.79% Admixed American · 430/54,426 alleles

Filtering AF 0.728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.704%

Overall 0.0764% 1,216/1,591,436 alleles · rare exomes 1,119/1,439,136 · genomes 97/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.79%	127
South Asian	0.641%	156
East Asian	0.355%	282
Remaining individualsnot grpmax-eligible	0.0894%	1,119
Middle Eastern	0.0835%	1,197
African / African-American	0.0137%	7,308
European (non-Finnish)	0.000341%	293,013

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.Arg1441=
Coding: c.4321A>C
MANE Select: NM_017934
dbSNP: rs148337691
Type: single nucleotide variant
Location: chr6:78946760 (GRCh38)

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

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-arg1441 (accessed [today's date]).

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