Is PHIP p.Ala662Pro (c.1984G>C) pathogenic?

PHIP p.Ala662Pro (c.1984G>C) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHIP p.Ala662Pro (c.1984G>C)?

PHIP p.Ala662Pro (c.1984G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PHIP p.Ala662Pro (c.1984G>C) in the general population?

PHIP p.Ala662Pro (c.1984G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Ala662Pro (c.1984G>C)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

PHIP p.Ala662Pro

c.1984G>C · rs536304988 · VCV3212208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · 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	0.0969	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.13	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 2.7	GERP 1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 11 kb · p 7.6e-13 · regional, not allelic
Overall
CADD	18.63	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.Ala662Pro
Coding: c.1984G>C
MANE Select: NM_017934
dbSNP: rs536304988
Type: single nucleotide variant
Location: chr6:78998287 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 662: the 'disordered' region; 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.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
PHIP p.Gly412Ser 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-ala662pro (accessed [today's date]).

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