Is PHIP p.Arg110Ser (c.328C>A) pathogenic?

PHIP p.Arg110Ser (c.328C>A) is classified Pathogenic in PHIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-02). AlphaMissense: likely pathogenic (0.9987); No allele count reported in gnomAD v4.1 (AN 1,611,668); Associated with PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome.

How common is PHIP p.Arg110Ser (c.328C>A) in the general population?

PHIP p.Arg110Ser (c.328C>A) is no allele count reported in gnomAD v4.1 (AN 1,611,668) (gnomAD).

What do computational predictors say about PHIP p.Arg110Ser (c.328C>A)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

PHIP p.Arg110Ser

Q: What condition is associated with PHIP p.Arg110Ser (c.328C>A)?

PHIP p.Arg110Ser (c.328C>A) 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.328C>A · rs768324201 · VCV545397

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,668)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic ✓ concordant with ClinVar · top 5% in PHIP
REVEL	0.482	indeterminate
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 51 kb · p 1.8e-17 · regional, not allelic
Overall
CADD	28.2	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

No allele count reported in gnomAD v4.1 (AN 1,611,668). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHIP
Protein: p.Arg110Ser
Coding: c.328C>A
MANE Select: NM_017934
dbSNP: rs768324201
Type: single nucleotide variant
Location: chr6:79060680 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 110: a UniProt-annotated variant site (in chujans; uncertain significance)

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

Similar variants

PHIP p.Arg110Cys Pathogenic/Likely pathogenic ★★ same residue
PHIP p.Arg110His Pathogenic ★ ⚠ same residue
PHIP p.Arg110Leu Uncertain significance ★ ⚠ same residue
PHIP p.Arg178Ter Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg255Ter Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg396Ter Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg503Ter Pathogenic/Likely pathogenic ★★ same condition
PHIP p.Arg721Ter Pathogenic/Likely pathogenic ★★ same condition

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-arg110ser (accessed [today's date]).

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