Is ENPP7 p.Val451Met (c.1351G>A) pathogenic?

ENPP7 p.Val451Met (c.1351G>A) is classified Likely benign in ENPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0883); Ultra-rare (popmax 0.0579%, eas).

How common is ENPP7 p.Val451Met (c.1351G>A) in the general population?

ENPP7 p.Val451Met (c.1351G>A) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

What do computational predictors say about ENPP7 p.Val451Met (c.1351G>A)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

ENPP7 p.Val451Met

c.1351G>A · rs782454569 · VCV2468571

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.79	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 -0.45	GERP -3.1
Regional constraint	o/e 0.98	unconstrained · MANE · 4,516 bp · p 0.7 · regional, not allelic
Overall
CADD	4.412	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

Grpmax group 0.0579% East Asian · 26/44,884 alleles

Filtering AF 0.0405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.00422% 68/1,612,718 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,726
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.00314%	31,892
Admixed American	0.00167%	60,012
South Asian	0.0011%	91,090

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ENPP7
Protein: p.Val451Met
Coding: c.1351G>A
MANE Select: NM_178543
dbSNP: rs782454569
Type: single nucleotide variant
Location: chr17:79738020 (GRCh38)
Gene constraint: LOEUF 1.471 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.15 · 2 PDB

Full ENPP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENPP7 p.Ala174Val Uncertain significance ★ ⚠ same type
ENPP7 p.Ala231Thr Uncertain significance ★ ⚠ same type
ENPP7 p.Ala322Thr Uncertain significance ★ ⚠ same type
ENPP7 p.Ala368Thr Uncertain significance ★ ⚠ same type
ENPP7 p.Ala407Pro Uncertain significance ★ ⚠ same type
ENPP7 p.Ala458Thr Uncertain significance ★ ⚠ same type
ENPP7 p.Ala5Val Uncertain significance ★ ⚠ same type
ENPP7 p.Arg156Gln 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/enpp7-p-val451met (accessed [today's date]).

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