Is ENTPD7 p.Phe200Ser (c.599T>C) pathogenic?

ENTPD7 p.Phe200Ser (c.599T>C) is classified Uncertain significance in ENTPD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.8958); Very rare (popmax 0.00667%, afr).

How common is ENTPD7 p.Phe200Ser (c.599T>C) in the general population?

ENTPD7 p.Phe200Ser (c.599T>C) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about ENTPD7 p.Phe200Ser (c.599T>C)?

AlphaMissense predicts likely pathogenic (score 0.8958) — an in-silico prediction, not a clinical call.

ENTPD7 p.Phe200Ser

c.599T>C · rs201287793 · VCV3089112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8958	likely pathogenic
REVEL	0.244	benign-leaning
SaProt	LLR -9.40	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 41 kb · p 0.0028 · regional, not allelic
Overall
CADD	27.9	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 0.00667% African / African-American · 5/74,976 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00155% 25/1,613,986 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,995
South Asian	0.00659%	15,180
East Asian	0.00223%	44,862
European (non-Finnish)	0.0011%	90,766

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: ENTPD7
Protein: p.Phe200Ser
Coding: c.599T>C
MANE Select: NM_020354
dbSNP: rs201287793
Type: single nucleotide variant
Location: chr10:99685842 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.57

Full ENTPD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX15 c.*2742A>G Uncertain significance ★ same type
COX15 c.*3086G>T Uncertain significance ★ same type
COX15 c.*3330A>G Uncertain significance ★ same type
COX15 c.*3362T>C Uncertain significance ★ same type
COX15 c.*3670G>A Uncertain significance ★ same type
COX15 c.*3729C>G Uncertain significance ★ same type
COX15 c.*4110T>G Uncertain significance ★ same type
COX15 c.*4435A>G 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/entpd7-p-phe200ser (accessed [today's date]).

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