Is PHIP p.Val1647= (c.4941T>A) pathogenic?

PHIP p.Val1647= (c.4941T>A) is classified Conflicting classifications of pathogenicity in PHIP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-05). Ultra-rare (popmax 0.0164%, mid).

How common is PHIP p.Val1647= (c.4941T>A) in the general population?

PHIP p.Val1647= (c.4941T>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PHIP p.Val1647=

c.4941T>A · rs1369466541 · VCV794565

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

⚠ 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
Pangolin	Δ0.21	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 0.93	GERP -2.7, phastCons 0.9
Overall
CADD	6.536	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00062% 10/1,613,788 alleles · ultra-rare exomes 9/1,461,746 · genomes 1/152,042 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00333%	29,991
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.000424%	235,984

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.Val1647=
Coding: c.4941T>A
MANE Select: NM_017934
dbSNP: rs1369466541
Type: single nucleotide variant
Location: chr6:78941218 (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-val1647 (accessed [today's date]).

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