Is PHIP p.Ser1524= (c.4572T>A) pathogenic?

PHIP p.Ser1524= (c.4572T>A) is classified Benign/Likely benign in PHIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-01). Ultra-rare (popmax 0.0267%, afr).

How common is PHIP p.Ser1524= (c.4572T>A) in the general population?

PHIP p.Ser1524= (c.4572T>A) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

PHIP p.Ser1524=

c.4572T>A · rs764553734 · VCV2904178

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

⚠ 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 1.6	GERP -5.7, phastCons 1
Overall
CADD	5.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,902 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,612,518 alleles · ultra-rare exomes 9/1,460,328 · genomes 12/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,745
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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.Ser1524=
Coding: c.4572T>A
MANE Select: NM_017934
dbSNP: rs764553734
Type: single nucleotide variant
Location: chr6:78946059 (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-ser1524 (accessed [today's date]).

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