Is PHIP p.Ala407Ser (c.1219G>T) pathogenic?

PHIP p.Ala407Ser (c.1219G>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely benign (0.0775); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHIP p.Ala407Ser (c.1219G>T)?

PHIP p.Ala407Ser (c.1219G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHIP p.Ala407Ser (c.1219G>T) in the general population?

PHIP p.Ala407Ser (c.1219G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Ala407Ser (c.1219G>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

PHIP p.Ala407Ser

c.1219G>T · VCV4627384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -4.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 22 kb · p 1e-18 · regional, not allelic
Overall
CADD	19.06	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ala407Ser
Coding: c.1219G>T
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:79016560 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 407: a UniProt-annotated variant site (in chujans)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHIP p.Ala407Gly Uncertain significance ★ ⚠ same residue
PHIP p.Arg160Gly Uncertain significance ★★ ⚠ same condition
PHIP p.Arg346Gln Uncertain significance ★★ ⚠ same condition
PHIP p.Arg691Leu Uncertain significance ★★ ⚠ same condition
PHIP p.Arg799Ile Uncertain significance ★★ ⚠ same condition
PHIP p.Arg837Thr Uncertain significance ★★ ⚠ same condition
PHIP p.Asn795His Uncertain significance ★★ ⚠ same condition
PHIP p.Gln638Glu Uncertain significance ★★ ⚠ 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-ala407ser (accessed [today's date]).

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