Is ENTPD6 p.Arg264Cys (c.790C>T) pathogenic?

ENTPD6 p.Arg264Cys (c.790C>T) is classified Uncertain significance in ENTPD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.1753); Ultra-rare (popmax 0.0166%, mid).

How common is ENTPD6 p.Arg264Cys (c.790C>T) in the general population?

ENTPD6 p.Arg264Cys (c.790C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about ENTPD6 p.Arg264Cys (c.790C>T)?

AlphaMissense predicts likely benign (score 0.1753) — an in-silico prediction, not a clinical call.

ENTPD6 p.Arg264Cys

c.790C>T · rs370052316 · VCV3089107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1753	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -11.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.6, phastCons 0.29
Regional constraint	o/e 0.97	unconstrained · MANE · 19 kb · p 0.5 · regional, not allelic
Overall
CADD	21.0	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 0.0166% Middle Eastern · 1/6,038 alleles

Filtering AF 0.00523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00477%

Overall 0.00539% 86/1,594,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,038
Remaining individualsnot grpmax-eligible	0.0113%	8,823
European (non-Finnish)	0.00641%	15,611
South Asian	0.00229%	43,757
Finnishnot grpmax-eligible	0.00161%	62,288

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: ENTPD6
Protein: p.Arg264Cys
Coding: c.790C>T
MANE Select: NM_001247
dbSNP: rs370052316
Type: single nucleotide variant
Location: chr20:25216728 (GRCh38)
Gene constraint: LOEUF 0.949 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21

Full ENTPD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD6 p.Arg264His Uncertain significance ★ ⚠ same residue
ENTPD6 p.Phe428= Benign ★★ same type
ENTPD6 p.Val436Ile Likely benign ★★ same type
ENTPD6 p.Ala305Val Uncertain significance ★ ⚠ same type
ENTPD6 p.Ala337Thr Uncertain significance ★ ⚠ same type
ENTPD6 p.Ala390Val Uncertain significance ★ ⚠ same type
ENTPD6 p.Ala397Val Uncertain significance ★ ⚠ same type
ENTPD6 p.Ala411Thr 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/entpd6-p-arg264cys (accessed [today's date]).

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