Is ENPP7 p.Ser417Phe (c.1250C>T) pathogenic?

ENPP7 p.Ser417Phe (c.1250C>T) is classified Uncertain significance in ENPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1298); Very rare (popmax 0.00891%, eas).

How common is ENPP7 p.Ser417Phe (c.1250C>T) in the general population?

ENPP7 p.Ser417Phe (c.1250C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ENPP7 p.Ser417Phe (c.1250C>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

ENPP7 p.Ser417Phe

c.1250C>T · rs782484935 · VCV3089034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.66	GERP -1.2, phastCons 0.003
Regional constraint	o/e 0.98	unconstrained · MANE · 4,516 bp · p 0.7 · regional, not allelic
Overall
CADD	14.63	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 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,461,470 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.0016%	62,498

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.Ser417Phe
Coding: c.1250C>T
MANE Select: NM_178543
dbSNP: rs782484935
Type: single nucleotide variant
Location: chr17:79737919 (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-ser417phe (accessed [today's date]).

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