Is PHIP p.Arg1441Ser (c.4323G>T) pathogenic?

PHIP p.Arg1441Ser (c.4323G>T) is classified Benign/Likely benign in PHIP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.6334); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with PHIP p.Arg1441Ser (c.4323G>T)?

PHIP p.Arg1441Ser (c.4323G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHIP p.Arg1441Ser (c.4323G>T) in the general population?

PHIP p.Arg1441Ser (c.4323G>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about PHIP p.Arg1441Ser (c.4323G>T)?

AlphaMissense predicts likely pathogenic (score 0.6334) — an in-silico prediction, not a clinical call.

PHIP p.Arg1441Ser

c.4323G>T · rs141705771 · VCV2142348

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6334 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ 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	0.6334	likely pathogenic
REVEL	0.122	moderately benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.61	GERP -0.34, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 9,095 bp · p 7e-13 · regional, not allelic
Overall
CADD	21.5	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 0.0167% Middle Eastern · 1/5,990 alleles

Filtering AF 0.00882% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00826%

Overall 0.00925% 147/1,589,972 alleles · ultra-rare exomes 137/1,437,926 · genomes 10/152,046 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,990
Admixed American	0.013%	7,718
South Asian	0.0127%	7,894
European (non-Finnish)	0.0103%	9,684
Remaining individualsnot grpmax-eligible	0.00651%	15,364
African / African-American	0.00412%	24,275

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.Arg1441Ser
Coding: c.4323G>T
MANE Select: NM_017934
dbSNP: rs141705771
Type: single nucleotide variant
Location: chr6:78946758 (GRCh38)

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

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-arg1441ser (accessed [today's date]).

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