Is ENTPD7 p.Phe292Ile (c.874T>A) pathogenic?

ENTPD7 p.Phe292Ile (c.874T>A) is classified Uncertain significance in ENTPD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.6721); Ultra-rare (popmax 0.0147%, afr).

How common is ENTPD7 p.Phe292Ile (c.874T>A) in the general population?

ENTPD7 p.Phe292Ile (c.874T>A) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about ENTPD7 p.Phe292Ile (c.874T>A)?

AlphaMissense predicts likely pathogenic (score 0.6721) — an in-silico prediction, not a clinical call.

ENTPD7 p.Phe292Ile

c.874T>A · VCV3845063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6721	likely pathogenic
REVEL	0.225	benign-leaning
SaProt	LLR -9.12	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 41 kb · p 0.0028 · regional, not allelic
Overall
CADD	23.5	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 0.0147% African / African-American · 11/74,880 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00093% 15/1,613,690 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,807
Admixed American	0.00334%	29,973
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Phe292Ile
Coding: c.874T>A
MANE Select: NM_020354
Type: single nucleotide variant
Location: chr10:99695986 (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-phe292ile (accessed [today's date]).

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