Is ENTPD4 p.Pro613Leu (c.1838C>T) pathogenic?

ENTPD4 p.Pro613Leu (c.1838C>T) is classified Uncertain significance in ENTPD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0766); Rare (popmax 0.101%, sas).

How common is ENTPD4 p.Pro613Leu (c.1838C>T) in the general population?

ENTPD4 p.Pro613Leu (c.1838C>T) is rare (popmax 0.101%, sas) (gnomAD).

What do computational predictors say about ENTPD4 p.Pro613Leu (c.1838C>T)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

ENTPD4 p.Pro613Leu

c.1838C>T · rs760898941 · VCV3089082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.41	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 3.3	GERP 6.6, phastCons 0.44
Regional constraint	o/e 1.00	unconstrained · MANE · 17 kb · p 0.91 · regional, not allelic
Overall
CADD	17.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% South Asian · 91/89,878 alleles

Filtering AF 0.0844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0781%

Overall 0.0165% 265/1,602,764 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.101%	988
Admixed American	0.019%	5,265
European (non-Finnish)	0.013%	7,676
Remaining individualsnot grpmax-eligible	0.0113%	8,856
African / African-American	0.00268%	37,318
East Asian	0.00226%	44,280

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: ENTPD4
Protein: p.Pro613Leu
Coding: c.1838C>T
MANE Select: NM_004901
dbSNP: rs760898941
Type: single nucleotide variant
Location: chr8:23432939 (GRCh38)
Gene constraint: LOEUF 0.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.51 · 1 PDB

Full ENTPD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENTPD4 p.Ala167Glu Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala214Thr Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala246Gly Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala267Val Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala280Val Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala462Glu Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala478Thr Uncertain significance ★ ⚠ same type
ENTPD4 p.Ala547Val 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/entpd4-p-pro613leu (accessed [today's date]).

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