Is PHIP p.Ala973Val (c.2918C>T) pathogenic?

PHIP p.Ala973Val (c.2918C>T) is classified Uncertain significance in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: ambiguous (0.549); Absent from gnomAD v4.1.

How common is PHIP p.Ala973Val (c.2918C>T) in the general population?

PHIP p.Ala973Val (c.2918C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHIP p.Ala973Val (c.2918C>T)?

AlphaMissense predicts ambiguous (score 0.549) — an in-silico prediction, not a clinical call.

PHIP p.Ala973Val

c.2918C>T · rs1767489395 · VCV1312345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.549 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ 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	0.549	ambiguous
REVEL	0.204	benign-leaning
SaProt	LLR -7.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 20 kb · p 9.1e-16 · regional, not allelic
Overall
CADD	25.2	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

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.Ala973Val
Coding: c.2918C>T
MANE Select: NM_017934
dbSNP: rs1767489395
Type: single nucleotide variant
Location: chr6:78970860 (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-ala973val (accessed [today's date]).

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