Is PHIP p.Arg968Ter (c.2902C>T) pathogenic?

PHIP p.Arg968Ter (c.2902C>T) is classified Pathogenic/Likely pathogenic in PHIP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-21). Very rare (popmax 0.00017%, nfe); Associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome.

How common is PHIP p.Arg968Ter (c.2902C>T) in the general population?

PHIP p.Arg968Ter (c.2902C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

PHIP p.Arg968Ter

Q: What condition is associated with PHIP p.Arg968Ter (c.2902C>T)?

PHIP p.Arg968Ter (c.2902C>T) is associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (ClinVar).

Q: How is PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2902C>T · rs200788163 · VCV523846

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome

⚠ 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.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.8	GERP 2.2, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,174,120 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,602,582 alleles · very rare exomes 2/1,450,560 · genomes 1/152,022 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,066
European (non-Finnish)grpmax	0.00017%	587,061

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg968Ter
Coding: c.2902C>T
MANE Select: NM_017934
dbSNP: rs200788163
Type: single nucleotide variant
Location: chr6:78970876 (GRCh38)

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

Disease context

For PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Infancy, Neonatal

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-arg968ter (accessed [today's date]).

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