Is PHIP p.Gly1069Ala (c.3206G>C) pathogenic?

PHIP p.Gly1069Ala (c.3206G>C) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: likely pathogenic (0.9272); Absent from gnomAD v4.1.

How common is PHIP p.Gly1069Ala (c.3206G>C) in the general population?

PHIP p.Gly1069Ala (c.3206G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Gly1069Ala (c.3206G>C)?

AlphaMissense predicts likely pathogenic (score 0.9272) — an in-silico prediction, not a clinical call.

PHIP p.Gly1069Ala

c.3206G>C · VCV3359901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9272 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.9272	likely pathogenic
REVEL	0.182	moderately benign-leaning
SaProt	LLR -11.16	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.36	loss · gain 0.06 · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 20 kb · p 9.1e-16 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHIP
Protein: p.Gly1069Ala
Coding: c.3206G>C
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:78966056 (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-gly1069ala (accessed [today's date]).

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