Is HIVEP2 p.Phe2002Val (c.6004T>G) pathogenic?

HIVEP2 p.Phe2002Val (c.6004T>G) is classified Uncertain significance in HIVEP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-24). AlphaMissense: likely pathogenic (0.8756); Absent from gnomAD v4.1.

How common is HIVEP2 p.Phe2002Val (c.6004T>G) in the general population?

HIVEP2 p.Phe2002Val (c.6004T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HIVEP2 p.Phe2002Val (c.6004T>G)?

AlphaMissense predicts likely pathogenic (score 0.8756) — an in-silico prediction, not a clinical call.

HIVEP2 p.Phe2002Val

c.6004T>G · rs2482770222 · VCV2682267

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8756	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 8,438 bp · p 0.008 · regional, not allelic
Overall
CADD	24.4	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: HIVEP2
Protein: p.Phe2002Val
Coding: c.6004T>G
MANE Select: NM_006734
dbSNP: rs2482770222
Type: single nucleotide variant
Location: chr6:142760284 (GRCh38)
Gene constraint: LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.43

Full HIVEP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HIVEP2 p.Arg1979Ter Pathogenic ★★ same type
HIVEP2 p.Arg2223Ter Pathogenic ★★ same type
HIVEP2 p.Arg943Ter Pathogenic ★★ same type
HIVEP2 p.Gln1138Ter Pathogenic ★★ same type
HIVEP2 p.Ala1501Asp Uncertain significance ★★ same type
HIVEP2 p.Ala437Ser Uncertain significance ★★ ⚠ same type
HIVEP2 p.Arg1497Gln Uncertain significance ★★ ⚠ same type
HIVEP2 p.Arg1794Cys Uncertain significance ★★ ⚠ same type

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/hivep2-p-phe2002val (accessed [today's date]).

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